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

Nat Immunol. 2012 Dec 23. doi: 10.1038/ni.2508. [Epub ahead of print]

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

Raetz M, Hwang SH, Wilhelm CL, Kirkland D, Benson A, Sturge CR, Mirpuri J, Vaishnava S, Hou B, Defranco AL, Gilpin CJ, Hooper LV, Yarovinsky F.

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

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.

 PMID: 23263554 [PubMed - as supplied by publisher]