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.

Cross-Talk between T Cells and NK Cells Generates Rapid Effector Responses to Plasmodium falciparum -Infected Erythrocytes

“…Alternatively, the differences seen in the various studies may reflect genuine heterogeneity in gdT cell responses among individuals or populations, reflecting the known inter-and intrapopulation diversity in numbers and TCR repertoires of gd + T cells (23). The strong abTCR + CD4 + T cell IFN-g response that we observed after 2-6 d of P. falciparum-infected RBC activation is highly consistent with previous reports in naive humans (13,14,24), with evidence for cross-reactive priming of malaria-reactive T cells by a diverse array of commonly encountered micro-organisms (13) and with data from murine infection models, indicating that ab + T cells can play a crucial role in the IFN-g response to primary infections (25)(26)(27). It is difficult to predict whether such cross-reactive responses would be beneficial should these individuals become infected with malaria; naive adults show very variable responses to primary malaria infections with some making very rapid, and partially protective, proinflammatory responses, whereas others make little or no inflammatory response and develop rapidly escalating parasitemia (28,29).…”

ShiA Abrogates the Innate T-Cell Response toShigella flexneriInfection

“…Furthermore, we observe that there are significantly more T cells at the site of wild-type and ⌬shiA strain infection than at the site of ShiA ϩ strain infection. A role for T cells in the innate immune response to Shigella infection was recently suggested by Le-Barillec et al (20). Our results suggest that in S. flexneri infections, ShiA down-regulates an innate inflammatory response that includes the recruitment of T cells.…”

“…IL-17, IL-6, MIP-2, and KC induce PMN maturation and migration (18,21,44). In addition, to date, one study has addressed the involvement of T cells in the innate immune response to Shigella infection (20). Our expression data indicated that T-cell-associated cytokines are elevated in FIG.…”

MyD88-Dependent IFN-γ Production by NK Cells Is Key for Control ofLegionella pneumophilaInfection

“…NK cell-derived IFN-␥ has been shown to be critical in the resolution of other bacterial infections (51,52). In the context of Lpn infection, a critical role of IFN-␥ has been demonstrated (13,53).…”