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Roles for T and NK Cells in the Innate Immune Response to Shigella flexneri

Abstract : Shigella flexneri, an enteroinvasive Gram-negative bacterium, is responsible for the worldwide endemic form of bacillary dysentery. The host response to primary infection is characterized by the induction of an acute inflammation, which is accompanied by polymorphonuclear cell (PMN) infiltration, resulting in massive destruction of the colonic mucosa. However, PMN play a major role in the recovery from primary infection, by restricting the bacterial infection at the intestinal mucosa. In this study, we assessed the roles for T and NK cells in the control of primary S. flexneri infection, using an alymphoid mouse strain (Rag null gamma(c) null) devoid of B, T, and NK cells. Using the mouse pulmonary model of Shigella infection, we showed that alymphoid Rag null gamma(c) null mice were highly susceptible to S. flexneri infection in comparison with wild-type (wt) mice. Whereas PMN recruitment upon infection was similar, macrophage recruitment and production of proinflammatory cytokines were significantly decreased in Rag null gamma(c) null mice compared with wt mice. Upon selective engraftment of Rag null gamma(c) null mice with polyclonal alphabeta T cells, but not with alphabeta T cells from IFN-gamma null , S. flexneri infection could be subsequently controlled. Rag null mice devoid of B and T cells but harboring NK cells could control infection. Local IFN-gamma production by T and NK cells recruited to the lung was demonstrated in S. flexneri-infected wt mice. These data demonstrate that both alphabeta T cells and NK cells contribute to the early control of S. flexneri infection through amplification of an inflammatory response. This cellular lymphocyte redundancy assures IFN-gamma production, which is central to innate immunity against Shigella infection.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02875015
Contributor : Armelle Phalipon <>
Submitted on : Friday, June 19, 2020 - 12:41:06 PM
Last modification on : Wednesday, July 29, 2020 - 11:10:47 AM

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Karine Le-Barillec, Joao Gamelas Magalhaes, Erwan Corcuff, Audrey Thuizat, Philippe Sansonetti, et al.. Roles for T and NK Cells in the Innate Immune Response to Shigella flexneri. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2005, 175 (3), pp.1735-1740. ⟨10.4049/jimmunol.175.3.1735⟩. ⟨pasteur-02875015⟩

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