The Experts below are selected from a list of 299811 Experts worldwide ranked by ideXlab platform

Sankar Ghosh - One of the best experts on this subject based on the ideXlab platform.

  • toll like Receptor 11 tlr11 interacts with flagellin and profilin through disparate mechanisms
    PLOS ONE, 2016
    Co-Authors: Matthew S Hayden, Hirotsugu Hatai, Alice Lepelley, Wangyong Zeng, Sankar Ghosh
    Abstract:

    Toll-Like Receptors (TLRs) are innate immune Receptors that sense a variety of pathogen-associated molecular patterns (PAMPs) by interacting with them and subsequently initiating signal transduction cascades that elicit immune responses. TLR11 has been shown to interact with two known protein PAMPs: Salmonella and E. coli flagellin FliC and Toxoplasma gondii profilin-like protein. Given the highly divergent biology of these pathogens recognized by TLR11, it is unclear whether common mechanisms are used to recognize these distinct protein PAMPs. Here we show that TLR11 interacts with these two PAMPs using different Receptor domains. Furthermore, TLR11 binding to flagellin and profilin exhibits differential dependency on pH and Receptor ectodomain cleavage.

  • recognition of profilin by toll like Receptor 12 is critical for host resistance to toxoplasma gondii
    Immunity, 2013
    Co-Authors: Alicia A Koblansky, Alan Sher, Sara Hieny, Dragana Jankovic, Waradon Sungnak, Ramkumar Mathur, Matthew S Hayden, Shizuo Akira, Sankar Ghosh
    Abstract:

    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.

Hirotsugu Hatai - One of the best experts on this subject based on the ideXlab platform.

  • toll like Receptor 11 tlr11 interacts with flagellin and profilin through disparate mechanisms
    PLOS ONE, 2016
    Co-Authors: Matthew S Hayden, Hirotsugu Hatai, Alice Lepelley, Wangyong Zeng, Sankar Ghosh
    Abstract:

    Toll-Like Receptors (TLRs) are innate immune Receptors that sense a variety of pathogen-associated molecular patterns (PAMPs) by interacting with them and subsequently initiating signal transduction cascades that elicit immune responses. TLR11 has been shown to interact with two known protein PAMPs: Salmonella and E. coli flagellin FliC and Toxoplasma gondii profilin-like protein. Given the highly divergent biology of these pathogens recognized by TLR11, it is unclear whether common mechanisms are used to recognize these distinct protein PAMPs. Here we show that TLR11 interacts with these two PAMPs using different Receptor domains. Furthermore, TLR11 binding to flagellin and profilin exhibits differential dependency on pH and Receptor ectodomain cleavage.

Matthew S Hayden - One of the best experts on this subject based on the ideXlab platform.

  • toll like Receptor 11 tlr11 interacts with flagellin and profilin through disparate mechanisms
    PLOS ONE, 2016
    Co-Authors: Matthew S Hayden, Hirotsugu Hatai, Alice Lepelley, Wangyong Zeng, Sankar Ghosh
    Abstract:

    Toll-Like Receptors (TLRs) are innate immune Receptors that sense a variety of pathogen-associated molecular patterns (PAMPs) by interacting with them and subsequently initiating signal transduction cascades that elicit immune responses. TLR11 has been shown to interact with two known protein PAMPs: Salmonella and E. coli flagellin FliC and Toxoplasma gondii profilin-like protein. Given the highly divergent biology of these pathogens recognized by TLR11, it is unclear whether common mechanisms are used to recognize these distinct protein PAMPs. Here we show that TLR11 interacts with these two PAMPs using different Receptor domains. Furthermore, TLR11 binding to flagellin and profilin exhibits differential dependency on pH and Receptor ectodomain cleavage.

  • recognition of profilin by toll like Receptor 12 is critical for host resistance to toxoplasma gondii
    Immunity, 2013
    Co-Authors: Alicia A Koblansky, Alan Sher, Sara Hieny, Dragana Jankovic, Waradon Sungnak, Ramkumar Mathur, Matthew S Hayden, Shizuo Akira, Sankar Ghosh
    Abstract:

    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.

Felix Yarovinsky - One of the best experts on this subject based on the ideXlab platform.

  • gut commensal bacteria direct a protective immune response against toxoplasma gondii
    Cell Host & Microbe, 2009
    Co-Authors: Alicia Benson, Reed Pifer, Cassie L Behrendt, Lora V Hooper, Felix Yarovinsky
    Abstract:

    Toxoplasma gondii is a universally distributed pathogen that infects over one billion people worldwide. Host resistance to this protozoan parasite depends on a Th1 immune response with potent production of the cytokines interleukin-12 and interferon gamma. Although Toll-Like Receptor 11 (TLR11) plays a major role in controlling Th1 immunity to this pathogen in mice, this innate immune Receptor is nonfunctional in humans, and the mechanisms of TLR11-independent sensing of T. gondii remain elusive. Here, we show that oral infection by T. gondii triggers a TLR11-independent but MyD88-dependent Th1 response that is impaired in TLR2xTLR4 double knockout and TLR9 single knockout mice. These mucosal innate and adaptive immune responses to T. gondii rely on the indirect stimulation of dendritic cells by normal gut microflora. Thus, our results reveal that gut commensal bacteria can serve as molecular adjuvants during parasitic infection, providing indirect immunostimulation that protects against T. gondii in the absence of TLR11.

Lora V Hooper - One of the best experts on this subject based on the ideXlab platform.

  • gut commensal bacteria direct a protective immune response against toxoplasma gondii
    Cell Host & Microbe, 2009
    Co-Authors: Alicia Benson, Reed Pifer, Cassie L Behrendt, Lora V Hooper, Felix Yarovinsky
    Abstract:

    Toxoplasma gondii is a universally distributed pathogen that infects over one billion people worldwide. Host resistance to this protozoan parasite depends on a Th1 immune response with potent production of the cytokines interleukin-12 and interferon gamma. Although Toll-Like Receptor 11 (TLR11) plays a major role in controlling Th1 immunity to this pathogen in mice, this innate immune Receptor is nonfunctional in humans, and the mechanisms of TLR11-independent sensing of T. gondii remain elusive. Here, we show that oral infection by T. gondii triggers a TLR11-independent but MyD88-dependent Th1 response that is impaired in TLR2xTLR4 double knockout and TLR9 single knockout mice. These mucosal innate and adaptive immune responses to T. gondii rely on the indirect stimulation of dendritic cells by normal gut microflora. Thus, our results reveal that gut commensal bacteria can serve as molecular adjuvants during parasitic infection, providing indirect immunostimulation that protects against T. gondii in the absence of TLR11.