The Experts below are selected from a list of 140994 Experts worldwide ranked by ideXlab platform
Gabriel Nunez - One of the best experts on this subject based on the ideXlab platform.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis , we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β–deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1beta maturation, showed unimpaired IL-1beta production and importantly, were considerably less susceptible to infection than IL-1beta deficient mice. Together our findings reveal a major role for IL-1beta in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
Sara Hieny - One of the best experts on this subject based on the ideXlab platform.
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recognition of profilin by toll like receptor 12 is critical for Host Resistance to toxoplasma gondii
Immunity, 2013Co-Authors: Alicia A Koblansky, Alan Sher, Sara Hieny, Dragana Jankovic, Waradon Sungnak, Ramkumar Mathur, Matthew S Hayden, Shizuo Akira, Sankar GhoshAbstract:Summary Toll-like receptor 11 (TLR11) recognizes T. gondii profilin (TgPRF) and is required for interleukin-12 production and induction of immune responses that limit cyst burden in Toxoplasma gondii -infected mice. However, TLR11 only modestly affects survival of T. gondii -challenged mice. We report that TLR12, a previously uncharacterized TLR, also recognized TgPRF. TLR12 was sufficient for recognition of TgPRF by plasmacytoid dendritic cells (pDCs), whereas TLR11 and TLR12 were both required in macrophages and conventional DCs. In contrast to TLR11, TLR12-deficient mice succumb rapidly to T. gondii infection. TLR12-dependent induction of IL-12 and IFN-α in pDCs led to production of IFN-γ by NK cells. Consistent with this observation, the partial Resistance of Tlr11 −/− mice is lost upon pDC or NK cell depletion. Thus, TLR12 is critical for the innate immune response to T. gondii , and this TLR may promote Host Resistance by triggering pDC and NK cell function.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis , we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β–deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1beta maturation, showed unimpaired IL-1beta production and importantly, were considerably less susceptible to infection than IL-1beta deficient mice. Together our findings reveal a major role for IL-1beta in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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the function of gamma interferon inducible gtp binding protein igtp in Host Resistance to toxoplasma gondii is stat1 dependent and requires expression in both hematopoietic and nonhematopoietic cellular compartments
Infection and Immunity, 2002Co-Authors: Carmen M Collazo, Sara Hieny, Patricia Caspar, Gregory A Taylor, George S Yap, Carl G Feng, Alan SherAbstract:IGTP is a member of the 47-kDa family of gamma interferon (IFN-gamma)-induced GTPases. We have previously shown that IGTP is critical for Host Resistance to Toxoplasma gondii infection. In the present study, we demonstrate that T. gondii-induced IGTP expression in vivo and IFN-gamma-driven synthesis of the protein in vitro are dependent on Stat1. Consistent with this observation, Stat1-deficient animals succumbed to T. gondii infection with the same rapid kinetics as IGTP(-/-) mice. To ascertain the cellular levels at which IGTP functions in Host control of acute infection, we constructed reciprocal bone marrow chimeras between IGTP-deficient and wild-type mice. Resistance to infection was observed only when IGTP was present in both hematopoietic and nonhematopoietic compartments. To assess the possible contribution of IGTP to the maintenance of parasite latency, partial chemotherapy was used to allow the establishment of chronic infection in IGTP-deficient animals. Upon cessation of drug treatment, these animals showed delayed mortality compared with similarly infected and treated IFN-gamma-deficient or inducible nitric oxide synthase-deficient mice, which succumbed rapidly. Parallel experiments performed with drug-treated bone marrow chimeras supported a role for the hematopoietic compartment in this NO-dependent, IGTP-independent control of chronic infection. Taken together, our findings demonstrate that Host Resistance mediated by IGTP is a Stat1-induced function which in the case of T. gondii acts predominantly to restrict acute as opposed to chronic infection. This effector mechanism requires expression of IGTP in cells of both hematopoietic and nonhematopoietic origin. In contrast, in latent infection, hematopoietically derived cells mediate Resistance by means of a largely NO-dependent pathway.
Patricia Caspar - One of the best experts on this subject based on the ideXlab platform.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis , we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β–deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1beta maturation, showed unimpaired IL-1beta production and importantly, were considerably less susceptible to infection than IL-1beta deficient mice. Together our findings reveal a major role for IL-1beta in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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the function of gamma interferon inducible gtp binding protein igtp in Host Resistance to toxoplasma gondii is stat1 dependent and requires expression in both hematopoietic and nonhematopoietic cellular compartments
Infection and Immunity, 2002Co-Authors: Carmen M Collazo, Sara Hieny, Patricia Caspar, Gregory A Taylor, George S Yap, Carl G Feng, Alan SherAbstract:IGTP is a member of the 47-kDa family of gamma interferon (IFN-gamma)-induced GTPases. We have previously shown that IGTP is critical for Host Resistance to Toxoplasma gondii infection. In the present study, we demonstrate that T. gondii-induced IGTP expression in vivo and IFN-gamma-driven synthesis of the protein in vitro are dependent on Stat1. Consistent with this observation, Stat1-deficient animals succumbed to T. gondii infection with the same rapid kinetics as IGTP(-/-) mice. To ascertain the cellular levels at which IGTP functions in Host control of acute infection, we constructed reciprocal bone marrow chimeras between IGTP-deficient and wild-type mice. Resistance to infection was observed only when IGTP was present in both hematopoietic and nonhematopoietic compartments. To assess the possible contribution of IGTP to the maintenance of parasite latency, partial chemotherapy was used to allow the establishment of chronic infection in IGTP-deficient animals. Upon cessation of drug treatment, these animals showed delayed mortality compared with similarly infected and treated IFN-gamma-deficient or inducible nitric oxide synthase-deficient mice, which succumbed rapidly. Parallel experiments performed with drug-treated bone marrow chimeras supported a role for the hematopoietic compartment in this NO-dependent, IGTP-independent control of chronic infection. Taken together, our findings demonstrate that Host Resistance mediated by IGTP is a Stat1-induced function which in the case of T. gondii acts predominantly to restrict acute as opposed to chronic infection. This effector mechanism requires expression of IGTP in cells of both hematopoietic and nonhematopoietic origin. In contrast, in latent infection, hematopoietically derived cells mediate Resistance by means of a largely NO-dependent pathway.
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perforin mediated cytolysis plays a limited role in Host Resistance to toxoplasma gondii
Journal of Immunology, 1997Co-Authors: Eric Y Denkers, Patricia Caspar, George S Yap, Tanya Schartonkersten, Hugues Charest, Barbara A Butcher, S Heiny, Alan SherAbstract:Resistance of perforin knockout (PKO) mice to infection with Toxoplasma gondii was assessed in models of acute infection and during chronic disease. PKO mice vaccinated with the attenuated mutant, ts-4, displayed severely defective CTL responses against tachyzoite-infected targets. Lysis of the NK target, YAC-1, was also severely impaired in PKO mice following ts-4 vaccination. In contrast, wild-type mice developed high levels of CTL and NK lytic activity after ts-4 vaccination. Despite severely defective lytic activity, vaccinated PKO animals were completely resistant to challenge with the virulent strain RH, which normally causes a lethal acute infection. Resistance was attributable to production of IFN-gamma, which remained unimpaired in the PKO animals. In contrast, when PKO mice were infected with low virulence parasite strain ME49, which progresses to the cyst-forming stage after passage through an acute phase, accelerated mortality was observed beginning at 75 days postinfection. A three- to fourfold increase in brain cyst numbers was also found by day 30 in infected PKO animals. Nevertheless, the PKO strain produced normal levels of IFN-gamma after ME49 infection, ruling out impaired production of the latter cytokine as a cause of increased susceptibility. Together, these results show that perforin-dependent cytolytic function is not required for Host Resistance to lethal acute infection in preimmunized animals, but that the latter activity contributes to the control of infection during the chronic stage.
Katrin D Mayerbarber - One of the best experts on this subject based on the ideXlab platform.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis , we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β–deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1beta maturation, showed unimpaired IL-1beta production and importantly, were considerably less susceptible to infection than IL-1beta deficient mice. Together our findings reveal a major role for IL-1beta in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
Allen W Cheever - One of the best experts on this subject based on the ideXlab platform.
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mannose binding lectin regulates Host Resistance and pathology during experimental infection with trypanosoma cruzi
PLOS ONE, 2012Co-Authors: Ester Roffe, Amanda K Gibson, Kazue Takahashi, Mario Steindel, Antonio Gigliotti Rothfuchs, Allen W Cheever, Alan Sher, Alan R B Ezekowitz, Andre BaficaAbstract:Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for Host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas’ disease, it is currently unknown whether MBL plays a role in Host Resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas’ disease. In this study we employed MBL−/− mice to assess the role of MBL in Resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas’ disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL−/− mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL−/− mice. Importantly, MBL−/− mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating Host Resistance and cardiac inflammation during infection with a major human pathogen.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis , we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1β–deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1β signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1β expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1β maturation, showed unimpaired IL-1β production and importantly, were considerably less susceptible to infection than IL-1β deficient mice. Together our findings reveal a major role for IL-1β in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.
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cutting edge caspase 1 independent il 1β production is critical for Host Resistance to mycobacterium tuberculosis and does not require tlr signaling in vivo
Journal of Immunology, 2010Co-Authors: Katrin D Mayerbarber, Allen W Cheever, Daniel L Barber, Kevin Shenderov, Sandra White, Mark S Wilson, David Kugler, Sara Hieny, Patricia Caspar, Gabriel NunezAbstract:To investigate the respective contributions of TLR versus IL-1R mediated signals in MyD88 dependent control of Mycobacterium tuberculosis, we compared the outcome of M. tuberculosis infection in MyD88, TRIF/MyD88, IL-1R1, and IL-1beta-deficient mice. All four strains displayed acute mortality with highly increased pulmonary bacterial burden suggesting a major role for IL-1beta signaling in determining the MyD88 dependent phenotype. Unexpectedly, the infected MyD88 and TRIF/MyD88-deficient mice, rather than being defective in IL-1beta expression, displayed increased cytokine levels relative to wild-type animals. Similarly, infected mice deficient in caspase-1 and ASC, which have critical functions in inflammasome-mediated IL-1beta maturation, showed unimpaired IL-1beta production and importantly, were considerably less susceptible to infection than IL-1beta deficient mice. Together our findings reveal a major role for IL-1beta in Host Resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1.