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Michal A Olszewski - One of the best experts on this subject based on the ideXlab platform.
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card9 is required for classical macrophage activation and the induction of protective immunity against Pulmonary Cryptococcosis
Mbio, 2020Co-Authors: Althea Campuzano, Natalia Castrolopez, Amanda J Martinez, Michal A Olszewski, Anutosh Ganguly, Chrissy Leopold M Wager, Chiungyu Hung, Floyd L WormleyAbstract:ABSTRACT Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against Cryptococcus neoformans, an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients. However, the effect of CARD9 deficiency on the induction of protective immune responses against C. neoformans is unknown. Immunization with a C. neoformans mutant that overexpresses the transcription factor zinc finger 2, denoted LW10, results in protection against an otherwise lethal challenge with wild-type (WT) C. neoformans. Our results showed that CARD9 is essential for the induction of vaccine-mediated immunity against C. neoformans infection. We observed significant decreases in interleukin-17 (IL-17) production and significant increases in Th2-type cytokine (IL-4, IL-5, and IL-13) production in CARD9-deficient mice after inoculation with strain LW10. While leukocyte infiltration to the lungs of CARD9-deficient mice was similar in LW10 and WT C. neoformans-infected mice, macrophages derived from CARD9-deficient mice inherently skewed toward an M2 activation phenotype, were unable to contain the growth of LW10, and failed to produce nitric oxide in response to infection with LW10 or stimulation with lipopolysaccharide. These results suggest that CARD9-mediated signaling is required for M1 macrophage activation and fungicidal activity necessary for the induction of vaccine-mediated immunity against C. neoformans. IMPORTANCECryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans.
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CARD9 Is Required for Classical Macrophage Activation and the Induction of Protective Immunity against Pulmonary Cryptococcosis
'American Society for Microbiology', 2020Co-Authors: Althea Campuzano, Amanda J Martinez, Michal A Olszewski, Anutosh Ganguly, Chiungyu Hung, Natalia Castro-lopez, Chrissy Leopold Wager, Floyd L WormleyAbstract:Cryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans.Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against Cryptococcus neoformans, an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients. However, the effect of CARD9 deficiency on the induction of protective immune responses against C. neoformans is unknown. Immunization with a C. neoformans mutant that overexpresses the transcription factor zinc finger 2, denoted LW10, results in protection against an otherwise lethal challenge with wild-type (WT) C. neoformans. Our results showed that CARD9 is essential for the induction of vaccine-mediated immunity against C. neoformans infection. We observed significant decreases in interleukin-17 (IL-17) production and significant increases in Th2-type cytokine (IL-4, IL-5, and IL-13) production in CARD9-deficient mice after inoculation with strain LW10. While leukocyte infiltration to the lungs of CARD9-deficient mice was similar in LW10 and WT C. neoformans-infected mice, macrophages derived from CARD9-deficient mice inherently skewed toward an M2 activation phenotype, were unable to contain the growth of LW10, and failed to produce nitric oxide in response to infection with LW10 or stimulation with lipopolysaccharide. These results suggest that CARD9-mediated signaling is required for M1 macrophage activation and fungicidal activity necessary for the induction of vaccine-mediated immunity against C. neoformans
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insights into the mechanisms of protective immunity against cryptococcus neoformans infection using a mouse model of Pulmonary Cryptococcosis
PLOS ONE, 2009Co-Authors: Karen L Wozniak, Michal A Olszewski, Sailatha Ravi, Sandra Macias, Mattie L Young, Chad Steele, Floyd L WormleyAbstract:Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-γ-producing C. neoformans strain, H99γ, results in complete protection against a second Pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against Pulmonary Cryptococcosis in mice immunized with C. neoformans strain H99γ compared to mice immunized with heat-killed C. neoformans (HKC.n.). Mice immunized with C. neoformans strain H99γ had significantly reduced Pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against Pulmonary Cryptococcosis was associated with increased Pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of Pulmonary inflammation, which protected the lungs from severe allergic bronchoPulmonary mycosis (ABPM)-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL)-4 receptor, IL-12p40, IL-12p35, IFN-γ, T cell and B cell deficient mice with C. neoformans strain H99γ demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99γ-mediated protective immune responses against Pulmonary C. neoformans infection. CD4+ T cells, CD11c+ cells, and Gr-1+ cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-γ or TNF-α in lungs of protected mice. In conclusion, immunization with C. neoformans strain H99γ results in the development of protective anti-cryptococcal immune responses that may be measured and subsequently used in the development of immune-based therapies to combat Pulmonary Cryptococcosis.
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role of granulocyte macrophage colony stimulating factor in host defense against Pulmonary cryptococcus neoformans infection during murine allergic bronchoPulmonary mycosis
American Journal of Pathology, 2007Co-Authors: Gwo Hsiao Chen, Michal A Olszewski, Roderick A Mcdonald, Galen B Toews, Gary B Huffnagle, Jason C Wells, Robert PaineAbstract:We investigated the role of granulocyte macrophage colony-stimulating factor (GM-CSF) in host defense in a murine model of Pulmonary Cryptococcosis induced by intratracheal inoculation of Cryptococcus neoformans. Pulmonary C. neoformans infection of C57BL/6 mice is an established model of an allergic bronchoPulmonary mycosis. Our objective was to determine whether GM-CSF regulates the Pulmonary Th2 immune response in C. neoformans-infected C57BL/6 mice. Long-term Pulmonary fungistasis was lost in GM-CSF knockout (GM−/−) mice, resulting in increased Pulmonary burden of fungi between weeks 3 and 5. GM-CSF was required for the early influx of macrophages and CD4 and CD8 T cells into the lungs but was not required later in the infection. Lack of GM-CSF also resulted in reduced eosinophil recruitment and delayed recruitment of mononuclear cells into the airspace. Macrophages from GM+/+ mice showed numerous hallmarks of alternatively activated macrophages: higher numbers of intracellular cryptococci, YM1 crystals, and induction of CCL17. These hallmarks are absent in macrophages from GM−/− mice. Mucus-producing goblet cells were abundantly present within the bronchial epithelial layer in GM+/+ mice but not in GM−/− mice at week 5 after infection. Production of both Th1 and Th2 cytokines was impaired in the absence of GM-CSF, consistent with both reduced C. neoformans clearance and absence of allergic lung pathology.
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the role of macrophage inflammatory protein 1α ccl3 in regulation of t cell mediated immunity to cryptococcus neoformans infection
Journal of Immunology, 2000Co-Authors: Michal A Olszewski, Dennis M Lindell, Roderick A Mcdonald, Gary B Huffnagle, Bethany B Moore, Donald N Cook, Galen B ToewsAbstract:Macrophage inflammatory protein-1α (MIP-1α/CCL3) is a CC chemokine required for optimal recruitment of leukocytes in response to cryptococcal Ags. MIP-1α is expressed in the lungs by day 6 post Cryptococcus neoformans infection and could play a role in the development of cell-mediated immunity. To address this possibility, wild-type (MIP-1α +/+ ) mice and MIP-1α knockout (MIP-1α −/− ) mice were infected intratracheally with a highly virulent strain of C. neoformans (145A). MIP-1α message was detected in the lungs on days 3, 7, and 14 in MIP-1α +/+ mice, but it was undetectable in MIP-1α −/− mice. On day 16, MIP-1α −/− mice had a 7-fold increase in C. neoformans burden in the lungs, but no decrease in Pulmonary leukocyte recruitment. MIP-1α +/+ and MIP-1α −/− mice had similar numbers of recruited lymphocytes and monocytes/macrophages. Notably, MIP-1α −/− mice had a significantly greater number of eosinophils. MIP-1α −/− mice had extremely high levels of serum IgE. This switch of immune response to a T 2 phenotype was associated with enhanced IL-4 and IL-13 expression in the lungs of MIP-1α −/− mice compared with MIP-1α +/+ mice. Progression of Pulmonary Cryptococcosis in the presence of nonprotective T 2 immunity resulted in profound lung damage in MIP-1α −/− mice (eosinophilic crystal deposition, destruction of lung parenchyma, and Pulmonary hemorrhage). Twelve-week survival was dramatically decreased in MIP-1α −/− mice. These studies, together with our previous studies, demonstrate that MIP-1α plays a role in both the afferent (T 1 /T 2 development) and efferent (T 1 -mediated leukocyte recruitment) phases of cell-mediated immunity to C. neoformans .
Galen B Toews - One of the best experts on this subject based on the ideXlab platform.
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role of granulocyte macrophage colony stimulating factor in host defense against Pulmonary cryptococcus neoformans infection during murine allergic bronchoPulmonary mycosis
American Journal of Pathology, 2007Co-Authors: Gwo Hsiao Chen, Michal A Olszewski, Roderick A Mcdonald, Galen B Toews, Gary B Huffnagle, Jason C Wells, Robert PaineAbstract:We investigated the role of granulocyte macrophage colony-stimulating factor (GM-CSF) in host defense in a murine model of Pulmonary Cryptococcosis induced by intratracheal inoculation of Cryptococcus neoformans. Pulmonary C. neoformans infection of C57BL/6 mice is an established model of an allergic bronchoPulmonary mycosis. Our objective was to determine whether GM-CSF regulates the Pulmonary Th2 immune response in C. neoformans-infected C57BL/6 mice. Long-term Pulmonary fungistasis was lost in GM-CSF knockout (GM−/−) mice, resulting in increased Pulmonary burden of fungi between weeks 3 and 5. GM-CSF was required for the early influx of macrophages and CD4 and CD8 T cells into the lungs but was not required later in the infection. Lack of GM-CSF also resulted in reduced eosinophil recruitment and delayed recruitment of mononuclear cells into the airspace. Macrophages from GM+/+ mice showed numerous hallmarks of alternatively activated macrophages: higher numbers of intracellular cryptococci, YM1 crystals, and induction of CCL17. These hallmarks are absent in macrophages from GM−/− mice. Mucus-producing goblet cells were abundantly present within the bronchial epithelial layer in GM+/+ mice but not in GM−/− mice at week 5 after infection. Production of both Th1 and Th2 cytokines was impaired in the absence of GM-CSF, consistent with both reduced C. neoformans clearance and absence of allergic lung pathology.
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distinct compartmentalization of cd4 t cell effector function versus proliferative capacity during Pulmonary Cryptococcosis
American Journal of Pathology, 2006Co-Authors: Dennis M Lindell, Thomas A Moore, Roderick A Mcdonald, Galen B Toews, Gary B HuffnagleAbstract:The activation and expansion of T cells and their acquisition of effector function are key steps in the development of the adaptive immune response. Most infections are predominantly outside of the lymphoid tissues, and it is unclear at what point developmentally and anatomically T cells acquire effector function in vivo. In these studies, we compared the activation and polarization of T cells during murine Pulmonary Cryptococcus neoformans infection in the secondary lymphoid tissues and at the site of primary infection. Few CD4+ and CD8+ T cells expressed an activated phenotype (CD44hi, CD25+, CD69+, CD62Llo, CD45RBlo) at the sites of clonal expansion (lymph nodes, spleen, and blood). In contrast, a high percentage of T cells expressed activation markers at the site of primary infection, the lungs. Additionally, the polarization of CD4+ T cells to interferon-γ-producing effector cells occurred at the site of infection, the lungs. CD4+ and CD8+ T cells from secondary lymphoid organs responded to TCR restimulation by proliferating, whereas T cells from the lungs proliferated poorly. This report demonstrates for the first time that T-cell activation and effector function in secondary lymphoid tissues during fungal infection is characteristically different from that at the site of primary infection.
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the role of macrophage inflammatory protein 1α ccl3 in regulation of t cell mediated immunity to cryptococcus neoformans infection
Journal of Immunology, 2000Co-Authors: Michal A Olszewski, Dennis M Lindell, Roderick A Mcdonald, Gary B Huffnagle, Bethany B Moore, Donald N Cook, Galen B ToewsAbstract:Macrophage inflammatory protein-1α (MIP-1α/CCL3) is a CC chemokine required for optimal recruitment of leukocytes in response to cryptococcal Ags. MIP-1α is expressed in the lungs by day 6 post Cryptococcus neoformans infection and could play a role in the development of cell-mediated immunity. To address this possibility, wild-type (MIP-1α +/+ ) mice and MIP-1α knockout (MIP-1α −/− ) mice were infected intratracheally with a highly virulent strain of C. neoformans (145A). MIP-1α message was detected in the lungs on days 3, 7, and 14 in MIP-1α +/+ mice, but it was undetectable in MIP-1α −/− mice. On day 16, MIP-1α −/− mice had a 7-fold increase in C. neoformans burden in the lungs, but no decrease in Pulmonary leukocyte recruitment. MIP-1α +/+ and MIP-1α −/− mice had similar numbers of recruited lymphocytes and monocytes/macrophages. Notably, MIP-1α −/− mice had a significantly greater number of eosinophils. MIP-1α −/− mice had extremely high levels of serum IgE. This switch of immune response to a T 2 phenotype was associated with enhanced IL-4 and IL-13 expression in the lungs of MIP-1α −/− mice compared with MIP-1α +/+ mice. Progression of Pulmonary Cryptococcosis in the presence of nonprotective T 2 immunity resulted in profound lung damage in MIP-1α −/− mice (eosinophilic crystal deposition, destruction of lung parenchyma, and Pulmonary hemorrhage). Twelve-week survival was dramatically decreased in MIP-1α −/− mice. These studies, together with our previous studies, demonstrate that MIP-1α plays a role in both the afferent (T 1 /T 2 development) and efferent (T 1 -mediated leukocyte recruitment) phases of cell-mediated immunity to C. neoformans .
Floyd L Wormley - One of the best experts on this subject based on the ideXlab platform.
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card9 is required for classical macrophage activation and the induction of protective immunity against Pulmonary Cryptococcosis
Mbio, 2020Co-Authors: Althea Campuzano, Natalia Castrolopez, Amanda J Martinez, Michal A Olszewski, Anutosh Ganguly, Chrissy Leopold M Wager, Chiungyu Hung, Floyd L WormleyAbstract:ABSTRACT Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against Cryptococcus neoformans, an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients. However, the effect of CARD9 deficiency on the induction of protective immune responses against C. neoformans is unknown. Immunization with a C. neoformans mutant that overexpresses the transcription factor zinc finger 2, denoted LW10, results in protection against an otherwise lethal challenge with wild-type (WT) C. neoformans. Our results showed that CARD9 is essential for the induction of vaccine-mediated immunity against C. neoformans infection. We observed significant decreases in interleukin-17 (IL-17) production and significant increases in Th2-type cytokine (IL-4, IL-5, and IL-13) production in CARD9-deficient mice after inoculation with strain LW10. While leukocyte infiltration to the lungs of CARD9-deficient mice was similar in LW10 and WT C. neoformans-infected mice, macrophages derived from CARD9-deficient mice inherently skewed toward an M2 activation phenotype, were unable to contain the growth of LW10, and failed to produce nitric oxide in response to infection with LW10 or stimulation with lipopolysaccharide. These results suggest that CARD9-mediated signaling is required for M1 macrophage activation and fungicidal activity necessary for the induction of vaccine-mediated immunity against C. neoformans. IMPORTANCECryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans.
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CARD9 Is Required for Classical Macrophage Activation and the Induction of Protective Immunity against Pulmonary Cryptococcosis
'American Society for Microbiology', 2020Co-Authors: Althea Campuzano, Amanda J Martinez, Michal A Olszewski, Anutosh Ganguly, Chiungyu Hung, Natalia Castro-lopez, Chrissy Leopold Wager, Floyd L WormleyAbstract:Cryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans.Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against Cryptococcus neoformans, an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients. However, the effect of CARD9 deficiency on the induction of protective immune responses against C. neoformans is unknown. Immunization with a C. neoformans mutant that overexpresses the transcription factor zinc finger 2, denoted LW10, results in protection against an otherwise lethal challenge with wild-type (WT) C. neoformans. Our results showed that CARD9 is essential for the induction of vaccine-mediated immunity against C. neoformans infection. We observed significant decreases in interleukin-17 (IL-17) production and significant increases in Th2-type cytokine (IL-4, IL-5, and IL-13) production in CARD9-deficient mice after inoculation with strain LW10. While leukocyte infiltration to the lungs of CARD9-deficient mice was similar in LW10 and WT C. neoformans-infected mice, macrophages derived from CARD9-deficient mice inherently skewed toward an M2 activation phenotype, were unable to contain the growth of LW10, and failed to produce nitric oxide in response to infection with LW10 or stimulation with lipopolysaccharide. These results suggest that CARD9-mediated signaling is required for M1 macrophage activation and fungicidal activity necessary for the induction of vaccine-mediated immunity against C. neoformans
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insights into the mechanisms of protective immunity against cryptococcus neoformans infection using a mouse model of Pulmonary Cryptococcosis
PLOS ONE, 2009Co-Authors: Karen L Wozniak, Michal A Olszewski, Sailatha Ravi, Sandra Macias, Mattie L Young, Chad Steele, Floyd L WormleyAbstract:Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown that immunization of BALB/c mice with an IFN-γ-producing C. neoformans strain, H99γ, results in complete protection against a second Pulmonary challenge with an otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated immune responses against Pulmonary Cryptococcosis in mice immunized with C. neoformans strain H99γ compared to mice immunized with heat-killed C. neoformans (HKC.n.). Mice immunized with C. neoformans strain H99γ had significantly reduced Pulmonary fungal burden post-secondary challenge compared to mice immunized with HKC.n. Protection against Pulmonary Cryptococcosis was associated with increased Pulmonary granulomatous formation and leukocyte infiltration followed by a rapid resolution of Pulmonary inflammation, which protected the lungs from severe allergic bronchoPulmonary mycosis (ABPM)-pathology that developed in the lungs of mice immunized with HKC.n. Pulmonary challenge of interleukin (IL)-4 receptor, IL-12p40, IL-12p35, IFN-γ, T cell and B cell deficient mice with C. neoformans strain H99γ demonstrated a requirement for Th1-type T cell-mediated immunity, but not B cell-mediated immunity, for the induction of H99γ-mediated protective immune responses against Pulmonary C. neoformans infection. CD4+ T cells, CD11c+ cells, and Gr-1+ cells were increased in both proportion and absolute number in protected mice. In addition, significantly increased production of Th1-type/pro-inflammatory cytokines and chemokines, and conversely, reduced Th2-type cytokine production was observed in the lungs of protected mice. Interestingly, protection was not associated with increased production of cytokines IFN-γ or TNF-α in lungs of protected mice. In conclusion, immunization with C. neoformans strain H99γ results in the development of protective anti-cryptococcal immune responses that may be measured and subsequently used in the development of immune-based therapies to combat Pulmonary Cryptococcosis.
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evaluation of host immune responses to Pulmonary Cryptococcosis using a temperature sensitive c neoformans calcineurin a mutant strain
Microbial Pathogenesis, 2005Co-Authors: Floyd L Wormley, Gary M Cox, John R PerfectAbstract:Abstract Cryptococcus neoformans is an opportunistic fungal pathogen that threatens individuals with impaired cell-mediated immunity (CMI). Presently, there are no standardized vaccines available to prevent cryptococcal infections and conventional anti-fungal drug therapy does not induce host immune reactivity and thus cannot efficiently resolve C. neoformans infections in immunocompromised individuals. The present study was designed to characterize Pulmonary immune responses following infection with an avirulent temperature-sensitive (ts) mutant, calcineurin A1 (cna1) compared to the pathogenic C. neoformans strain H99 and its potential to induce protective anti-cryptococcal immunity. Host CMI responses in cna1-inoculated mice were observed to be dose-dependent, and comprise increases in Pulmonary macrophages and CD4+ T lymphocytes. However, cytokine analysis demonstrated a mixed Pulmonary cytokine response (increases in IL-4, and MCP-1) with no induction of IFN-γ. Also, pre-immunization with the ts cna1 mutant did not result in protection from a subsequent secondary Pulmonary infection with the pathogenic C. neoformans strain H99. Taken together, these results suggest that host Pulmonary CMI responses to the ts cna1 mutant that is eventually eliminated from the host without the induction of IFN-γ appear to be dose-dependent, diverse, and require further stimulation to induce C. neoformans-specific Th1-type cytokine responses to resolve subsequent experimental Pulmonary cryptococcal infections.
Jay H Ryu - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary Cryptococcosis ct findings in immunocompetent patients
Radiology, 2005Co-Authors: Rebecca M Lindell, Hassan F Nadrous, Thomas E Hartman, Jay H RyuAbstract:PURPOSE: To evaluate retrospectively the computed tomographic (CT) findings in immunocompetent patients with Pulmonary Cryptococcosis. MATERIALS AND METHODS: Institutional review board approval was obtained with a waiver of informed consent, and the study complied with requirements of the Health Insurance Portability and Accountability Act. Chest CT scans of 10 immunocompetent patients with clinically proved Pulmonary Cryptococcosis were retrospectively reviewed by four reviewers in consensus. Criterion for diagnosis of Pulmonary Cryptococcosis was (a) the histopathologic presence of the organism at lung biopsy or (b) a positive culture of a respiratory specimen or positive serum cryptococcal antigen test with clinical or radiographic evidence of active Pulmonary infection. Patients included six women and four men ranging in age from 46 to 73 years (mean, 59 years). Scans were evaluated for nodules, masses, areas of ground-glass attenuation or of hazy increased attenuation, areas of consolidation, areas o...
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Pulmonary Cryptococcosis in nonimmunocompromised patients
Chest, 2003Co-Authors: Hassan F Nadrous, Vera S Antonios, Christine L Terrell, Jay H RyuAbstract:Background Cryptococcus neoformans can cause serious systemic infections requiring systemic antifungal therapy in immunocompromised hosts. However, isolated Pulmonary Cryptococcosis in nonimmunocompromised hosts has been reported to resolve spontaneously without treatment. Study objectives To determine the role of antifungal therapy in the management of isolated Pulmonary Cryptococcosis in nonimmunocompromised hosts. Design Retrospective study. Setting Tertiary care, referral medical center Patients Thirty-six nonimmunocompromised subjects with isolated Pulmonary Cryptococcosis who received diagnoses at the Mayo Clinic (Rochester, MN) from 1976 to 2001. Interventions None. Measurements and results Of 42 nonimmunocompromised subjects with cryptococcal infections, 36 (86%) had isolated Pulmonary Cryptococcosis. The mean (± SD) age of these 36 patients was 61 ± 15 years (range, 14 to 88 years), and the groups included 17 men (47%) and 19 women (53%). Twenty-four patients (67%) were symptomatic, and 12 patients (33%) were asymptomatic. The most common presenting symptoms were cough, dyspnea, and fever. Cultures of sputum and bronchial washings most commonly yielded the diagnosis. Cerebrospinal fluid examination was performed in 11 patients (31%) and was negative in all of them. Follow-up information was available on 25 patients (69%) with a median duration of 19 months (range, 1 to 330 months). Twenty-three of these patients (92%) had resolution of their disease (no treatment, 8 patients; surgical resection only, 6 patients; and antifungal therapy, 9 patients). The condition of the two remaining patients had improved. There was no documented treatment failure, relapse, dissemination, or death in any of these 25 patients. Conclusions Our findings suggest that an initial period of observation without the administration of antifungal therapy is a reasonable option for nonimmunocompromised subjects with Pulmonary Cryptococcosis in the absence of systemic symptoms or evidence of dissemination, as well as after surgical resection for focal cryptococcal pneumonia.
Yuan Zhang - One of the best experts on this subject based on the ideXlab platform.
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pleural fluid secondary to Pulmonary cryptococcal infection a case report and review of the literature
BMC Infectious Diseases, 2019Co-Authors: Yuan Zhang, Sean X Zhang, Julie B Trivedi, Adam Toll, Julie R Brahmer, Russell K Hales, Sarah Bonerigo, Mingying Zeng, Rex YungAbstract:Pulmonary Cryptococcosis (PC) is diagnosed with increasing incidence in recent years, but it does not commonly involve the pleural space. Here, we report a HIV-negative case with advanced stage IIIB non-small cell lung cancer (NSCLC) treated with radiation therapy presented with dyspnea, a new PET-positive lung mass and bilateral pleural effusion suspecting progressive cancer. However, the patient has been diagnosed as Pulmonary cryptococcal infection and successfully treated with oral fluconazole therapy. A 77-year-old male with advanced stage non-small cell lung cancer treated with combined chemo-radiation therapy who presented with progressive dyspnea, a new PET-positive left lower lobe lung mass and bilateral pleural effusions. Initial diagnostic thoracentesis and bronchoscopy yielded no cancer, but instead found yeast forms consistent with cryptococcal organisms in the transbronchial biopsies of the left lower lobe lung mass. Subsequent to this, the previously collected pleural fluid culture showed growth of Cryptococcus neoformans. The same sample of pleural effusion was tested and was found to be positive for crytococcal antigen (CrAg) by a lateral flow assay (LFA). The patient has been treated with oral fluconazole therapy resulting in gradual resolution of the nodular infiltrates. PC should be considered in immunosuppressed cancer patients. Additionally, concomitant pleural involvement in Pulmonary cryptococcal infections may occur. The incidence of false positive 18FDG-PET scans in granulomatous infections and the use of CrAg testing in pleural fluid to aid in diagnosis are reviewed.
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clinical analysis of 76 patients pathologically diagnosed with Pulmonary Cryptococcosis
European Respiratory Journal, 2012Co-Authors: Yuan Zhang, Yuxuan Zhang, Xueyuan Chen, Shanmei Wang, Xia Zhang, Rongxuan Zhang, Jingyun Shi, Rex YungAbstract:The aim of the present study was to investigate the clinical characteristics of Pulmonary Cryptococcosis patients in China, with analysis of immunocompetent and immunocompromised subjects. We performed a retrospective review of 76 patients diagnosed with tissue-confirmed Pulmonary Cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001–2010). Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. As of December 31, 2010, 71 cases showed total recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of 76). One HIV-positive case died of cryptococcal meningitis. Incidence of Pulmonary Cryptococcosis in China may be related to environmental fungal exposures. Most presented as asymptomatic peripheral lung lesions. False-positive 18FDG-PET examinations often lead to initial clinical misdiagnosis of cancer. Unlike immunocompromised or clinically symptomatic patients, all immunocompetent patients had a good response, either to fluconazole monotherapy or observation, with a tendency for spontaneous remissions in the asymptomatic immunocompetent subjects.
