Th17 Cells Are the Dominant T Cell Subtype Primed by <i>Shigella flexneri</i> Mediating Protective Immunity

Sellge, Gernot; Magalhães, João G.; Konradt, Christoph; Fritz, Jörg H.; Salgado-Pabón, Wilmara; Eberl, Gérard; Bandeira, António; Santo, James P. Di; Sansonetti, P; Phalipon, Armelle

doi:10.4049/jimmunol.0900978

Cited by 83 publications

(75 citation statements)

References 57 publications

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“…Human pathogens that reside within host cells and, like Chlamydia, induce natural immunity after infection include bacteria such as Salmonella, Shigella, Mycobacterium, and Yersinia, and parasites such as Leishmania (3,31,(48)(49)(50). Because immunity against these pathogens appears to be mediated by cellular and antibody responses, the approach described here could lead to the discovery of vaccines that have so far proved to be difficult to develop.…”

Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Natural immunity against obligate and/or facultative intracellular pathogens is usually mediated by both humoral and cellular immunity. The identification of those antigens stimulating both arms of the immune system is instrumental for vaccine discovery. Although high-throughput technologies have been applied for the discovery of antibody-inducing antigens, few examples of their application for T-cell antigens have been reported. We describe how the compilation of the immunome, here defined as the pool of immunogenic antigens inducing T- and B-cell responses in vivo, can lead to vaccine candidates against Chlamydia trachomatis . We selected 120 C. trachomatis proteins and assessed their immunogenicity using two parallel high-throughput approaches. Protein arrays were generated and screened with sera from C. trachomatis -infected patients to identify antibody-inducing antigens. Splenocytes from C. trachomatis -infected mice were stimulated with 79 proteins, and the frequency of antigen-specific CD4 + /IFN-γ + T cells was analyzed by flow cytometry. We identified 21 antibody-inducing antigens, 16 CD4 + /IFN-γ + –inducing antigens, and five antigens eliciting both types of responses. Assessment of their protective activity in a mouse model of Chlamydia muridarum lung infection led to the identification of seven antigens conferring partial protection when administered with LTK63/CpG adjuvant. Protection was largely the result of cellular immunity as assessed by CD4 + T-cell depletion. The seven antigens provided robust additive protection when combined in four-antigen combinations. This study paves the way for the development of an effective anti- Chlamydia vaccine and provides a general approach for the discovery of vaccines against other intracellular pathogens.

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Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…T-cell response [45][46][47] Recent studies report that in a murine model of acute bacterial infection with S. flexneri the T cell response is dominated by the induction of long-term memory Shigellaspecific Th17 cells that contribute to mediate protective immunity against reinfection [52] Now, new research shows an unexpected direct role for TLR2 signalling in T cells themselves, promoting the differentiation and proliferation of T helper 17 (T H 17) cells [50]. Taking into account these data and together with previous results from our own group about the high ability of PVM/MA to stimulate TLR2 [5] suggest that these …”

Section: Discussionmentioning

confidence: 99%

Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice

Camacho

Souza

Sánchez-Gómez

et al. 2011

Vaccine

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“…Indeed, acute inflammation has been associated with apoptotic cell death of T lymphocytes in rectal biopsies of infected individuals (8,9), impairment of dendritic cell (DC) recruitment to the site of Shigella infection in a model of human intestinal xenotransplant (10), and the predominant priming of Shigella-specific CD4 + Th17 cells conferring limited protection against reinfection in a murine model of infection (11). Evidence suggests that CD8 + T lymphocytes are not required for protective immunity (11). In fact, antigen-specific CD8…”

mentioning

confidence: 99%

Shigella impairs T lymphocyte dynamics in vivo

Salgado-Pabón

Celli

Arena

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The Gram-negative enteroinvasive bacterium Shigella flexneri is responsible for the endemic form of bacillary dysentery, an acute rectocolitis in humans. S. flexneri uses a type III secretion system to inject effector proteins into host cells, thus diverting cellular functions to its own benefit. Protective immunity to reinfection requires several rounds of infection to be elicited and is short-lasting, suggesting that S. flexneri interferes with the priming of specific immunity. Considering the key role played by T-lymphocyte trafficking in priming of adaptive immunity, we investigated the impact of S. flexneri on T-cell dynamics in vivo. By using two-photon microscopy to visualize bacterium-T-cell cross-talks in the lymph nodes, where the adaptive immunity is initiated, we provide evidence that S. flexneri, via its type III secretion system, impairs the migration pattern of CD4 + T cells independently of cognate recognition of bacterial antigens. We show that bacterial invasion of CD4 + T lymphocytes occurs in vivo, and results in cell migration arrest. In the absence of invasion, CD4+ T-cell migration parameters are also dramatically altered. Signals resulting from S. flexneri interactions with subcapsular sinus macrophages and dendritic cells, and recruitment of polymorphonuclear cells are likely to contribute to this phenomenon. These findings indicate that S. flexneri targets T lymphocytes in vivo and highlight the role of type III effector secretion in modulating host adaptive immune responses.host-pathogen cross-talks | imaging

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

Abstract: Material Supplementary 8.DC1http://www.jimmunol.org/content/suppl/2010/01/13/jimmunol.090097

Cited by 83 publications

References 57 publications

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice

Shigella impairs T lymphocyte dynamics in vivo

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