Parasite-induced T H 1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells

Megan Raetz, Sun Hee Hwang, Cara L. Wilhelm, Donna Kirkland, Alicia Benson, Carolyn R. Sturge, Julie Mirpuri, Shipra Vaishnava, Baidong Hou, Anthony L. Defranco, Christopher J. Gilpin, Lora V. Hooper, Felix Yarovinsky

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Activation of Toll-like receptors (TLRs) by pathogens triggers cytokine production and T cell activation, immune defense mechanisms that are linked to immunopathology. Here we show that IFN-γ production by CD4 + T H 1 cells during mucosal responses to the protozoan parasite Toxoplasma gondii resulted in dysbiosis and the elimination of Paneth cells. Paneth cell death led to loss of antimicrobial peptides and occurred in conjunction with uncontrolled expansion of the Enterobacteriaceae family of Gram-negative bacteria. The expanded intestinal bacteria were required for the parasite-induced intestinal pathology. The investigation of cell type-specific factors regulating T H 1 polarization during T. gondii infection identified the T cell-intrinsic TLR pathway as a major regulator of IFN-γ production in CD4 + T cells responsible for Paneth cell death, dysbiosis and intestinal immunopathology.

Original languageEnglish (US)
Pages (from-to)136-142
Number of pages7
JournalNature immunology
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Raetz, M., Hwang, S. H., Wilhelm, C. L., Kirkland, D., Benson, A., Sturge, C. R., Mirpuri, J., Vaishnava, S., Hou, B., Defranco, A. L., Gilpin, C. J., Hooper, L. V., & Yarovinsky, F. (2013). Parasite-induced T H 1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells. Nature immunology, 14(2), 136-142. https://doi.org/10.1038/ni.2508