Gut Commensal Bacteria Direct a Protective Immune Response against Toxoplasma gondii

Alicia Benson; Reed Pifer; Cassie L. Behrendt; Lora V. Hooper; Felix Yarovinsky

doi:10.1016/j.chom.2009.06.005

Gut Commensal Bacteria Direct a Protective Immune Response against Toxoplasma gondii

Alicia Benson, Reed Pifer, Cassie L. Behrendt, Lora V. Hooper, Felix Yarovinsky

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

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 γ. 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.

Original language	English (US)
Pages (from-to)	187-196
Number of pages	10
Journal	Cell Host and Microbe
Volume	6
Issue number	2
DOIs	https://doi.org/10.1016/j.chom.2009.06.005
State	Published - Aug 20 2009

Keywords

CELLIMMUNO
MICROBIO
MOLIMMUNO

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2009.06.005

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title = "Gut Commensal Bacteria Direct a Protective Immune Response against Toxoplasma gondii",

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 γ. 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.",

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author = "Alicia Benson and Reed Pifer and Behrendt, {Cassie L.} and Hooper, {Lora V.} and Felix Yarovinsky",

note = "Funding Information: The authors are grateful to Shipra Vaishnava and Cynthia A. Leifer for critically reading and discussing the manuscript. We also thank Daniel L. Barber for his input on T. gondii -specific CD4 + T cell recall responses and John Shelton for help with histology. This work was supported by the UT Southwestern Medical Center Endowed Scholars Program, by Award Number R21AI079371 (to F.Y.) from the National Institute of Allergy and Infectious Diseases (NIAID), by NIH R01 DK070855 to L.V.H., and by the Howard Hughes Medical Institute (L.V.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the National Institutes of Health. ",

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AU - Yarovinsky, Felix

N1 - Funding Information: The authors are grateful to Shipra Vaishnava and Cynthia A. Leifer for critically reading and discussing the manuscript. We also thank Daniel L. Barber for his input on T. gondii -specific CD4 + T cell recall responses and John Shelton for help with histology. This work was supported by the UT Southwestern Medical Center Endowed Scholars Program, by Award Number R21AI079371 (to F.Y.) from the National Institute of Allergy and Infectious Diseases (NIAID), by NIH R01 DK070855 to L.V.H., and by the Howard Hughes Medical Institute (L.V.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the National Institutes of Health.

PY - 2009/8/20

Y1 - 2009/8/20

N2 - 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 γ. 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.

AB - 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 γ. 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.

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Gut Commensal Bacteria Direct a Protective Immune Response against Toxoplasma gondii

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