The unexpected link between infection-induced apoptosis and a TH17 immune response.
Microbial pathogens can initiate MOMP in host cells and as such, initiate the mitochondrial pathway of apoptosis. Innate immune recognition of cells dying in this way by infection-induced apoptosis would involve recognition of ligands derived from the apoptotic host cell simultaneously with those derived from the infecting pathogen. The resultant signal transduction pathways engaged direct DCs to concomitantly synthesize TGF-β and IL-6, two cytokines that subsequently favor the differentiation of naïve CD4 T cells into T(h)17 cells. Citrobacter rodentium is one rodent pathogen that targets mitochondria and induces apoptosis, and blockade of apoptosis during enteric Citrobacter infection impairs the characteristic T(h)17 response in the intestinal LP. Here, we review these original findings. We discuss microbial infections other than Citrobacter that have been shown to induce T(h)17 responses, and we examine what is known about the ability of those pathogens to induce apoptosis. We also consider types of cell death other than apoptosis that can be triggered by microbial infection, and we highlight how little we know about the impact of various forms of cell death on the ensuing adaptive immune response.
Mount Sinai School of Medicine, Immunology Institute, Department of Medicine, 1425 Madison Ave., 12-20D, New York, NY 10029, USA.
Corinna F
CF
Brereton
J Magarian
JM
Blander
D000818:Animals; D017209:Apoptosis; D001419:Bacteria / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology*; D006801:Humans; D058504:Th17 Cells / Q000276:immunology*
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