Th17 Cells Are the Dominant T Cell Subtype Primed by Shigella flexneri Mediating Protective Immunity

作者：Gernot Sellge, João G. Magalhães, Christoph Konradt, Jörg H. Fritz, Wilmara Salgado‐Pabón, Gérard Eberl, António Bandeira, James P. Di Santo, Phillippe J. Sansonetti, Armelle Phalipon · 发表于：The Journal of Immunology · 年份：2010 · DOI：10.4049/jimmunol.0900978 · 被引用次数：91 · 研究领域：Psoriasis: Treatment and Pathogenesis、T-cell and B-cell Immunology、Dermatology and Skin Diseases

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.