The Experts below are selected from a list of 9870 Experts worldwide ranked by ideXlab platform
Mireia Pelegrin - One of the best experts on this subject based on the ideXlab platform.
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differential and sequential immunomodulatory role of neutrophils and ly6chi inflammatory monocytes during Antiviral Antibody therapy
Emerging microbes & infections, 2021Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. We previously showed a role for immune complexes (ICs) in the enhancement of Antiviral T-cell responses through FcγR-mediated activation of dendritic cells (DCs). Here we addressed how mAb therapy in retrovirus-infected mice affects the activation of neutrophils and inflammatory monocytes, two FcγR-expressing innate effector cells rapidly recruited to sites of infection. We found that both cell-types activated in vitro by viral ICs secreted chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV on neutrophils and inflammatory monocytes and enhanced their cytokines/chemokines secretion. Notably, upon Antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the Antiviral immune response by secreting Th1-type polarizing cytokines and chemokines, which occurred in a FcγRIV-dependent manner. Consistently, FcγRIV- blocking in mAb-treated, infected mice led to reduced immune protection. Our work provides new findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon Antiviral mAb therapy.
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immunomodulatory role of nk cells during Antiviral Antibody therapy
Vaccine, 2021Co-Authors: Mar Naranjogomez, Marine Cahen, Jennifer Lambour, Myriam Boyerclavel, Mireia PelegrinAbstract:Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this effect. NK cells are effector cells that are crucial to control viral propagation upon mAb treatment. However, their immunomodulatory activity during Antiviral mAb immunotherapies has been little studied. Our data reveal that the mAb treatment of infected mice preserves the functional activation of NK cells. Importantly, functional NK cells play an essential role in preventing immune dysfunction and inducing Antiviral protective immunity upon mAb therapy. Thus, NK cell depletion in mAb-treated, viral-infected mice leads to the upregulation of molecules involved in immunosuppressive pathways (i.e., PD-1, PD-L1 and CD39) on dendritic cells and T cells. NK cell depletion also abrogates the vaccinal effects induced by mAb therapy. Our data also reveal a role for IFNγ-producing NK cells in the enhancement of the B-cell responses through the potentiation of the B-cell helper properties of neutrophils. These findings suggest that preserved NK cell functions and counts might be required for achieving mAb-induced protective immunity. They open new prospects for improving Antiviral immunotherapies.
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differential and sequential immunomodulatory role of neutrophils and ly6chi inflammatory monocytes during Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. Using a mouse model of retroviral infection, we previously showed a crucial role for immune complexes (ICs) in the enhancement of T-cell responses through FcγR-mediated activation of dendritic cells (DCs). However, IC-FcγR interactions involve different cells of the immune system other than DCs such as neutrophils and monocytes. These two myeloid cell-types are innate effector cells rapidly recruited to sites of infection. In addition to being key cells to fight against invading pathogens, they are also endowed with immunomodulatory properties. While the role of DCs in enhancing Antiviral immune responses upon mAb treatment has been addressed in several studies, the role of neutrophils and monocytes has been much less studied. Here we addressed how mAb therapy affects the functional activation of neutrophils and inflammatory monocytes in retrovirus-infected mice. We found that both cell-types activated in vitro by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV expression on neutrophils and inflammatory monocytes and enhanced their cytokines and chemokines secretion. Notably, upon Antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the Antiviral immune response through the secretion of Th1-type polarizing cytokines and chemokines. Our work provides novel findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon Antiviral mAb therapy.
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functionally distinct neutrophils sequentially promote th1 type responses upon Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-FcγRs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects the functional activation of neutrophils. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRs upregulation. Similarly, infection and mAb-treatment upregulated FcγRs expression on neutrophils and enhanced their cytokines and chemokines secretion. FcγRs upregulation allowed to identify in vivo two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon Antiviral mAb therapy.
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different immunomodulatory role of ly6ghi and ly6gint neutrophils during Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-Fc{gamma}Rs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects neutrophils functional activation. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced Fc{gamma}Rs upregulation. Similarly, infection and mAb-treatment upregulated Fc{gamma}Rs expression on neutrophils and enhanced their cytokines and chemokines secretion. Fc{gamma}Rs upregulation allowed to identify in vivo two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon Antiviral mAb therapy.
Rolf M. Zinkernagel - One of the best experts on this subject based on the ideXlab platform.
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Antiviral Antibody responses: The two extremes of a wide spectrum
Nature Reviews Immunology, 2006Co-Authors: Lars Hangartner, Rolf M. Zinkernagel, Hans HengartnerAbstract:Viruses elicit a diverse spectrum of Antiviral Antibody responses. In this review, we discuss two widely used experimental model systems for viral infections - non-cytopathic lymphocytic choriomeningitis virus (LCMV) and acutely cytopathic vesicular stomatitis virus (VSV) - to analyse two fundamentally different types of Antiviral Antibody response. The basic principles found in these model infections are discussed in the context of other viral infections, and with regard to protective neutralizing versus non-protective enzyme-linked immunosorbent assay (ELISA)-detected Antibody responses. Issues of Antibody specificity, affinity and avidity, maturation and escape are discussed in the context of co-evolution of the host and viruses
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leflunomide mediated suppression of Antiviral Antibody and tcell responses differential restoration by uridine
Transplantation, 2001Co-Authors: Daniel D Pinschewer, Thomas Fehr, Adrian F Ochsenbein, Rolf M. ZinkernagelAbstract:Background. Leflunomide is an isoxazol derivative with immunosuppressive capacities in various experimental allo- and xenotransplantation models. Two main mechanisms of action have been described: Inhibition of pyrimidine de novo synthesis and impairment of tyrosine phosphorylation of different tyrosine kinases involved in receptor signaling via B cell and cytokine receptors. Materials and Methods. Interference of Leflunomide with the IgM Antibody responses to vesicular stomatitis virus (VSV, T-independent type 1), IgM to recombinant VSV glycoprotein (T-independent type 2), and IgG to lymphocytic choriomeningitis virus (LCMV, T-dependent) were analyzed whereas the cytotoxic T cell (CTL) response was examined after LCMV infection. Interference with the CD8 + T cell-mediated autoimmune diabetes in a transgenic mouse expressing the LCMV-glycoprotein in the pancreatic islets was studied as a model for T cell-mediated autoimmune diseases. Uridine substitution experiments were performed to differentiate between the above mentioned two mechanisms of action on different functions of the immune system in vivo. Results. Leflunomide at 35 mg/kg/day suppressed the humoral immune response against all antigens tested. Similar effects on T-independent compared to T-dependent Antibody responses required two to four times higher drug doses. CTL responses to LCMV were considerably impaired. Uridine substitution prevented lethal VSV encephalitis under Leflunomide treatment by restoring the neutralizing IgM and IgG responses. However, the inhibition of LCMV specific CTLs and suppression of CD8 + T cell-mediated autoimmune diabetes remained unaffected by additional uridine treatment. Conclusions. Leflunomide-mediated suppression of B cell and T helper cell activity but not of CTLs largely depends on inhibition of pyrimidine de novo synthesis.
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neutralizing Antiviral Antibody responses
Advances in Immunology, 2001Co-Authors: Rolf M. Zinkernagel, Alain Lamarre, Adrian Ciurea, Lukas Hunziker, Adrian F Ochsenbein, Kathy D Mccoy, Thomas Fehr, Martin F Bachmann, Ulrich Kalinke, Hans HengartnerAbstract:Publisher Summary Neutralizing antibodies are evolutionarily important effectors of immunity against viruses. Their evaluation has revealed a number of basic insights into specificity, rules of reactivity (tolerance), and memory—namely, (1) Specificity of neutralizing antibodies is defined by their capacity to distinguish between virus serotypes; (2) B cell reactivity is determined by antigen structure, concentration, and time of availability in secondary lymphoid organs; and (3) B cell memory is provided by elevated protective Antibody titers in serum that are depending on antigen stimulation. These perhaps slightly overstated rules are simple, correlate with in vivo evidence as well as clinical observations, and appear to largely demystify many speculations about antibodies and B cell physiology. The chapter also considers successful vaccines and compares them with those infectious diseases where efficient protective vaccines are lacking, it is striking to note that all successful vaccines induce high levels of neutralizing antibodies (nAbs) that are both necessary and sufficient to protect the host from disease. Successful vaccination against infectious diseases such as tuberculosis, leprosy, or HIV would require induction of additional long-lasting T cell responses to control infection.
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protective t cell independent Antiviral Antibody responses are dependent on complement
Journal of Experimental Medicine, 1999Co-Authors: Adrian F Ochsenbein, Michael C Carroll, Hans Hengartner, Daniel D Pinschewer, Bernhard Odermatt, Rolf M. ZinkernagelAbstract:Complement is part of the innate immune system and one of the first lines of host defense against infections. Its importance was evaluated in this study in virus infections in mice deficient either in soluble complement factors (C3−/−, C4−/−) or in the complement signaling complex (complement receptor [CR]2−/−, CD19−/−). The induction of the initial T cell–independent neutralizing immunoglobulin (Ig)M Antibody response to vesicular stomatitis virus (VSV), poliomyelitis virus, and recombinant vaccinia virus depended on efficient antigen trapping by CR3 and -4–expressing macrophages of the splenic marginal zone. Neutralizing IgM and IgG Antibody responses were largely independent of CR2-mediated stimulation of B cells when mice were infected with live virus. In contrast, immunizations with nonreplicating antigens revealed an important role of B cell stimulation via CR2 in the switch to IgG. The complement cascade was activated after infection with VSV via the classical pathway, and active complement cleavage products augmented the effector function of neutralizing IgM and IgG antibodies to VSV by a factor of 10–100. Absence of the early neutralizing Antibody responses, together with the reduced efficiency of neutralizing IgM in C3−/− mice, led to a drastically enhanced susceptibility to disease after infection with VSV.
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impairment and delay of neutralizing Antiviral Antibody responses by virus specific cytotoxic t cells
Journal of Immunology, 1993Co-Authors: Manuel Battegay, Hans Hengartner, Demetrius Moskophidis, H Waldner, Marieanne Brundler, Waiping Fungleung, Tak W Mak, Rolf M. ZinkernagelAbstract:After infection with some viruses that tend to persist, neutralizing antibodies are generated rather late, i.e., after 1 to 3 mo. This has been observed for HIV, Hepatitis B infection in man, or after infection with lymphocytic choriomeningitis virus (LCMV) in mice. In contrast, nonneutralizing antibodies to LCMV are generated by day 7 and reach high titers by day 10. This study attempts to evaluate reasons for late and low titered neutralizing Antibody responses. After a primary infection with low doses (10(2) plaque forming units) of the poorly cytopathic LCMV-WE, neutralizing antibodies were rarely produced at detectable levels before days 60 to 120. In vivo depletion of CD8+ CTL led to a marked enhancement and acceleration of kinetics of the neutralizing Antibody response. In contrast, nonneutralizing antibodies, including those specific for LCMV-GP carrying the neutralizing determinant, were detectable very early, i.e., 4 to 7 days after infection, with maximum titers usually by day 10 irrespective of the presence or absence of CTL. Mice completely lacking CD8+ T cells because of deletion by homologous recombination (CD8-/-) also exhibited neutralizing antibodies early by day 10 to 20, and by day 120 reached very high titers. The neurotropic isolate LCMV-ARMSTRONG induced low but significant titers of neutralizing antibodies relatively early (i.e., by days 7 to 10), whereas the lympho-viscerotrope mutant virus LCMV-ARMSTRONG Cl-13 did not. Early and effective CTL responses causing immunopathology (and immunosuppression) correlated with the absence of neutralizing antibodies. The discrepancy between the CTL-dependent inhibition of neutralizing versus unimpaired anti-GP ELISA responses cannot be explained by different Ag doses alone. Additionally, it may reflect different kinetics of the responses, whereby the later neutralizing responses possibly requiring IgG affinity maturation may be more susceptible to general immunosuppression; also B cells expressing neutralizing receptors, but not those with antibodies binding GP (or NP), may be actively infected, therefore they present viral peptides on class I MHC Ag and may become targets for anti-LCMV-specific CTL.
Hans Hengartner - One of the best experts on this subject based on the ideXlab platform.
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Antiviral Antibody responses: The two extremes of a wide spectrum
Nature Reviews Immunology, 2006Co-Authors: Lars Hangartner, Rolf M. Zinkernagel, Hans HengartnerAbstract:Viruses elicit a diverse spectrum of Antiviral Antibody responses. In this review, we discuss two widely used experimental model systems for viral infections - non-cytopathic lymphocytic choriomeningitis virus (LCMV) and acutely cytopathic vesicular stomatitis virus (VSV) - to analyse two fundamentally different types of Antiviral Antibody response. The basic principles found in these model infections are discussed in the context of other viral infections, and with regard to protective neutralizing versus non-protective enzyme-linked immunosorbent assay (ELISA)-detected Antibody responses. Issues of Antibody specificity, affinity and avidity, maturation and escape are discussed in the context of co-evolution of the host and viruses
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neutralizing Antiviral Antibody responses
Advances in Immunology, 2001Co-Authors: Rolf M. Zinkernagel, Alain Lamarre, Adrian Ciurea, Lukas Hunziker, Adrian F Ochsenbein, Kathy D Mccoy, Thomas Fehr, Martin F Bachmann, Ulrich Kalinke, Hans HengartnerAbstract:Publisher Summary Neutralizing antibodies are evolutionarily important effectors of immunity against viruses. Their evaluation has revealed a number of basic insights into specificity, rules of reactivity (tolerance), and memory—namely, (1) Specificity of neutralizing antibodies is defined by their capacity to distinguish between virus serotypes; (2) B cell reactivity is determined by antigen structure, concentration, and time of availability in secondary lymphoid organs; and (3) B cell memory is provided by elevated protective Antibody titers in serum that are depending on antigen stimulation. These perhaps slightly overstated rules are simple, correlate with in vivo evidence as well as clinical observations, and appear to largely demystify many speculations about antibodies and B cell physiology. The chapter also considers successful vaccines and compares them with those infectious diseases where efficient protective vaccines are lacking, it is striking to note that all successful vaccines induce high levels of neutralizing antibodies (nAbs) that are both necessary and sufficient to protect the host from disease. Successful vaccination against infectious diseases such as tuberculosis, leprosy, or HIV would require induction of additional long-lasting T cell responses to control infection.
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protective t cell independent Antiviral Antibody responses are dependent on complement
Journal of Experimental Medicine, 1999Co-Authors: Adrian F Ochsenbein, Michael C Carroll, Hans Hengartner, Daniel D Pinschewer, Bernhard Odermatt, Rolf M. ZinkernagelAbstract:Complement is part of the innate immune system and one of the first lines of host defense against infections. Its importance was evaluated in this study in virus infections in mice deficient either in soluble complement factors (C3−/−, C4−/−) or in the complement signaling complex (complement receptor [CR]2−/−, CD19−/−). The induction of the initial T cell–independent neutralizing immunoglobulin (Ig)M Antibody response to vesicular stomatitis virus (VSV), poliomyelitis virus, and recombinant vaccinia virus depended on efficient antigen trapping by CR3 and -4–expressing macrophages of the splenic marginal zone. Neutralizing IgM and IgG Antibody responses were largely independent of CR2-mediated stimulation of B cells when mice were infected with live virus. In contrast, immunizations with nonreplicating antigens revealed an important role of B cell stimulation via CR2 in the switch to IgG. The complement cascade was activated after infection with VSV via the classical pathway, and active complement cleavage products augmented the effector function of neutralizing IgM and IgG antibodies to VSV by a factor of 10–100. Absence of the early neutralizing Antibody responses, together with the reduced efficiency of neutralizing IgM in C3−/− mice, led to a drastically enhanced susceptibility to disease after infection with VSV.
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impairment and delay of neutralizing Antiviral Antibody responses by virus specific cytotoxic t cells
Journal of Immunology, 1993Co-Authors: Manuel Battegay, Hans Hengartner, Demetrius Moskophidis, H Waldner, Marieanne Brundler, Waiping Fungleung, Tak W Mak, Rolf M. ZinkernagelAbstract:After infection with some viruses that tend to persist, neutralizing antibodies are generated rather late, i.e., after 1 to 3 mo. This has been observed for HIV, Hepatitis B infection in man, or after infection with lymphocytic choriomeningitis virus (LCMV) in mice. In contrast, nonneutralizing antibodies to LCMV are generated by day 7 and reach high titers by day 10. This study attempts to evaluate reasons for late and low titered neutralizing Antibody responses. After a primary infection with low doses (10(2) plaque forming units) of the poorly cytopathic LCMV-WE, neutralizing antibodies were rarely produced at detectable levels before days 60 to 120. In vivo depletion of CD8+ CTL led to a marked enhancement and acceleration of kinetics of the neutralizing Antibody response. In contrast, nonneutralizing antibodies, including those specific for LCMV-GP carrying the neutralizing determinant, were detectable very early, i.e., 4 to 7 days after infection, with maximum titers usually by day 10 irrespective of the presence or absence of CTL. Mice completely lacking CD8+ T cells because of deletion by homologous recombination (CD8-/-) also exhibited neutralizing antibodies early by day 10 to 20, and by day 120 reached very high titers. The neurotropic isolate LCMV-ARMSTRONG induced low but significant titers of neutralizing antibodies relatively early (i.e., by days 7 to 10), whereas the lympho-viscerotrope mutant virus LCMV-ARMSTRONG Cl-13 did not. Early and effective CTL responses causing immunopathology (and immunosuppression) correlated with the absence of neutralizing antibodies. The discrepancy between the CTL-dependent inhibition of neutralizing versus unimpaired anti-GP ELISA responses cannot be explained by different Ag doses alone. Additionally, it may reflect different kinetics of the responses, whereby the later neutralizing responses possibly requiring IgG affinity maturation may be more susceptible to general immunosuppression; also B cells expressing neutralizing receptors, but not those with antibodies binding GP (or NP), may be actively infected, therefore they present viral peptides on class I MHC Ag and may become targets for anti-LCMV-specific CTL.
Mar Naranjogomez - One of the best experts on this subject based on the ideXlab platform.
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differential and sequential immunomodulatory role of neutrophils and ly6chi inflammatory monocytes during Antiviral Antibody therapy
Emerging microbes & infections, 2021Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. We previously showed a role for immune complexes (ICs) in the enhancement of Antiviral T-cell responses through FcγR-mediated activation of dendritic cells (DCs). Here we addressed how mAb therapy in retrovirus-infected mice affects the activation of neutrophils and inflammatory monocytes, two FcγR-expressing innate effector cells rapidly recruited to sites of infection. We found that both cell-types activated in vitro by viral ICs secreted chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV on neutrophils and inflammatory monocytes and enhanced their cytokines/chemokines secretion. Notably, upon Antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the Antiviral immune response by secreting Th1-type polarizing cytokines and chemokines, which occurred in a FcγRIV-dependent manner. Consistently, FcγRIV- blocking in mAb-treated, infected mice led to reduced immune protection. Our work provides new findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon Antiviral mAb therapy.
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immunomodulatory role of nk cells during Antiviral Antibody therapy
Vaccine, 2021Co-Authors: Mar Naranjogomez, Marine Cahen, Jennifer Lambour, Myriam Boyerclavel, Mireia PelegrinAbstract:Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this effect. NK cells are effector cells that are crucial to control viral propagation upon mAb treatment. However, their immunomodulatory activity during Antiviral mAb immunotherapies has been little studied. Our data reveal that the mAb treatment of infected mice preserves the functional activation of NK cells. Importantly, functional NK cells play an essential role in preventing immune dysfunction and inducing Antiviral protective immunity upon mAb therapy. Thus, NK cell depletion in mAb-treated, viral-infected mice leads to the upregulation of molecules involved in immunosuppressive pathways (i.e., PD-1, PD-L1 and CD39) on dendritic cells and T cells. NK cell depletion also abrogates the vaccinal effects induced by mAb therapy. Our data also reveal a role for IFNγ-producing NK cells in the enhancement of the B-cell responses through the potentiation of the B-cell helper properties of neutrophils. These findings suggest that preserved NK cell functions and counts might be required for achieving mAb-induced protective immunity. They open new prospects for improving Antiviral immunotherapies.
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differential and sequential immunomodulatory role of neutrophils and ly6chi inflammatory monocytes during Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. Using a mouse model of retroviral infection, we previously showed a crucial role for immune complexes (ICs) in the enhancement of T-cell responses through FcγR-mediated activation of dendritic cells (DCs). However, IC-FcγR interactions involve different cells of the immune system other than DCs such as neutrophils and monocytes. These two myeloid cell-types are innate effector cells rapidly recruited to sites of infection. In addition to being key cells to fight against invading pathogens, they are also endowed with immunomodulatory properties. While the role of DCs in enhancing Antiviral immune responses upon mAb treatment has been addressed in several studies, the role of neutrophils and monocytes has been much less studied. Here we addressed how mAb therapy affects the functional activation of neutrophils and inflammatory monocytes in retrovirus-infected mice. We found that both cell-types activated in vitro by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV expression on neutrophils and inflammatory monocytes and enhanced their cytokines and chemokines secretion. Notably, upon Antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the Antiviral immune response through the secretion of Th1-type polarizing cytokines and chemokines. Our work provides novel findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon Antiviral mAb therapy.
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functionally distinct neutrophils sequentially promote th1 type responses upon Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-FcγRs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects the functional activation of neutrophils. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRs upregulation. Similarly, infection and mAb-treatment upregulated FcγRs expression on neutrophils and enhanced their cytokines and chemokines secretion. FcγRs upregulation allowed to identify in vivo two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon Antiviral mAb therapy.
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different immunomodulatory role of ly6ghi and ly6gint neutrophils during Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-Fc{gamma}Rs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects neutrophils functional activation. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced Fc{gamma}Rs upregulation. Similarly, infection and mAb-treatment upregulated Fc{gamma}Rs expression on neutrophils and enhanced their cytokines and chemokines secretion. Fc{gamma}Rs upregulation allowed to identify in vivo two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon Antiviral mAb therapy.
Jennifer Lambour - One of the best experts on this subject based on the ideXlab platform.
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differential and sequential immunomodulatory role of neutrophils and ly6chi inflammatory monocytes during Antiviral Antibody therapy
Emerging microbes & infections, 2021Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. We previously showed a role for immune complexes (ICs) in the enhancement of Antiviral T-cell responses through FcγR-mediated activation of dendritic cells (DCs). Here we addressed how mAb therapy in retrovirus-infected mice affects the activation of neutrophils and inflammatory monocytes, two FcγR-expressing innate effector cells rapidly recruited to sites of infection. We found that both cell-types activated in vitro by viral ICs secreted chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV on neutrophils and inflammatory monocytes and enhanced their cytokines/chemokines secretion. Notably, upon Antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the Antiviral immune response by secreting Th1-type polarizing cytokines and chemokines, which occurred in a FcγRIV-dependent manner. Consistently, FcγRIV- blocking in mAb-treated, infected mice led to reduced immune protection. Our work provides new findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon Antiviral mAb therapy.
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immunomodulatory role of nk cells during Antiviral Antibody therapy
Vaccine, 2021Co-Authors: Mar Naranjogomez, Marine Cahen, Jennifer Lambour, Myriam Boyerclavel, Mireia PelegrinAbstract:Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this effect. NK cells are effector cells that are crucial to control viral propagation upon mAb treatment. However, their immunomodulatory activity during Antiviral mAb immunotherapies has been little studied. Our data reveal that the mAb treatment of infected mice preserves the functional activation of NK cells. Importantly, functional NK cells play an essential role in preventing immune dysfunction and inducing Antiviral protective immunity upon mAb therapy. Thus, NK cell depletion in mAb-treated, viral-infected mice leads to the upregulation of molecules involved in immunosuppressive pathways (i.e., PD-1, PD-L1 and CD39) on dendritic cells and T cells. NK cell depletion also abrogates the vaccinal effects induced by mAb therapy. Our data also reveal a role for IFNγ-producing NK cells in the enhancement of the B-cell responses through the potentiation of the B-cell helper properties of neutrophils. These findings suggest that preserved NK cell functions and counts might be required for achieving mAb-induced protective immunity. They open new prospects for improving Antiviral immunotherapies.
-
differential and sequential immunomodulatory role of neutrophils and ly6chi inflammatory monocytes during Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through Fc-FcγRs interactions. Using a mouse model of retroviral infection, we previously showed a crucial role for immune complexes (ICs) in the enhancement of T-cell responses through FcγR-mediated activation of dendritic cells (DCs). However, IC-FcγR interactions involve different cells of the immune system other than DCs such as neutrophils and monocytes. These two myeloid cell-types are innate effector cells rapidly recruited to sites of infection. In addition to being key cells to fight against invading pathogens, they are also endowed with immunomodulatory properties. While the role of DCs in enhancing Antiviral immune responses upon mAb treatment has been addressed in several studies, the role of neutrophils and monocytes has been much less studied. Here we addressed how mAb therapy affects the functional activation of neutrophils and inflammatory monocytes in retrovirus-infected mice. We found that both cell-types activated in vitro by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRIV upregulation. Similarly, infection and mAb-treatment upregulated FcγRIV expression on neutrophils and inflammatory monocytes and enhanced their cytokines and chemokines secretion. Notably, upon Antibody therapy neutrophils and inflammatory monocytes displayed distinct functional activation states and sequentially modulated the Antiviral immune response through the secretion of Th1-type polarizing cytokines and chemokines. Our work provides novel findings on the immunomodulatory role of neutrophils and monocytes in the enhancement of immune responses upon Antiviral mAb therapy.
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functionally distinct neutrophils sequentially promote th1 type responses upon Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-FcγRs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects the functional activation of neutrophils. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced FcγRs upregulation. Similarly, infection and mAb-treatment upregulated FcγRs expression on neutrophils and enhanced their cytokines and chemokines secretion. FcγRs upregulation allowed to identify in vivo two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon Antiviral mAb therapy.
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different immunomodulatory role of ly6ghi and ly6gint neutrophils during Antiviral Antibody therapy
bioRxiv, 2020Co-Authors: Jennifer Lambour, Mar Naranjogomez, Myriam Boyerclavel, Mireia PelegrinAbstract:Antiviral monoclonal antibodies (mAbs) can generate protective immunity through immune complexes (IC)-Fc{gamma}Rs interactions. We have shown the essential role of neutrophils in mAb-induced immunity of retrovirus-infected mice. Using this model, here we addressed how viral infection, with or without mAb therapy, affects neutrophils functional activation. We found that neutrophils activated by viral ICs secreted high levels of chemokines able to recruit monocytes and neutrophils themselves. Moreover, inflammatory cytokines potentiated chemokines and cytokines release by IC-activated cells and induced Fc{gamma}Rs upregulation. Similarly, infection and mAb-treatment upregulated Fc{gamma}Rs expression on neutrophils and enhanced their cytokines and chemokines secretion. Fc{gamma}Rs upregulation allowed to identify in vivo two splenic neutrophils subpopulations with distinct phenotypic and functional properties that differentially and sequentially collaborate with inflammatory monocytes to induce Th1-type responses in mAb-treated mice. Our work provides novel findings on the heterogeneity and the immunomodulatory role of neutrophils in the enhancement of immune responses upon Antiviral mAb therapy.