Th17 cells are the dominant T cell subtype primed by Shigella flexneri mediating protective immunity.
The T cell response to Shigella, the causative agent of bacillary dysentery, remains poorly understood. Using a murine model of infection, we report that Shigella flexneri primes predominately IL-17A- and IL-22-producing Th17 cells. Shigella-specific Th1 cells are only significantly induced on secondary infection, whereas specific Th2 and CD8(+) T cells are undetectable. Apart from Th17 cells that are primed in a MHC class II- and IL-6-dependent, but IL12/23p40-independent manner, we identified gammadelta T cells as an additional but minor source of IL-17A. Priming of IL-17A(+) gammadelta T cells is dependent on IL12/23p40, but independent of MHC-class II and IL-6. Th17 cells have emerged as important players in inflammatory, autoimmune, and infectious diseases. Among the yet unresolved questions is their role in long-term immunity to pathogens. In this study, we show that the elicited S. flexneri-specific Th17 pool gives rise to an enhanced recall response up to 12 mo after priming, suggesting the presence of a long-term memory state. The clearance of primary infection is impaired in the absence of T cells, but independently of IL-17A. However, after reinfection, IL-17A produced by S. flexneri-specific Th17 cells becomes important to ultimately restrict bacterial growth. These findings bring new insights into the adaptive immune response to Shigella infection and highlight the importance of pathogen-specific Th17 cell immunity for secondary immune protection.
Sellge
Gernot
G
Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France.
Magalhaes
Joao G
JG
Konradt
Christoph
C
Fritz
Jörg H
JH
Salgado-Pabon
Wilmara
W
Eberl
Gérard
G
Bandeira
Antonio
A
Di Santo
James P
JP
Sansonetti
Phillippe J
PJ
Phalipon
Armelle
A
D000818:Animals; D002478:Cells, Cultured; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012763:Shigella flexneri / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
D016056:Immunodominant Epitopes; D020381:Interleukin-17