Impaired dendritic cell functions because of depletion of natural killer cells disrupt antigen-specific immune responses in mice: restoration of adaptive immunity in natural killer-depleted mice by antigen-pulsed dendritic cell

Dendritic cells (DC) play a key role in establishing protective adaptive immunity in intracellular bacterial infections, but the cells influencing DC function in vivo remain unclear. In this study, we investigated the role of NK cells in modulating the function of DC using a murine Chlamydia infection model. We found that the NK cell-depleted mice showed exacerbated disease after respiratory tract Chlamydia muridarum infection, which was correlated with altered T cell cytokine profile. Furthermore, DC from C. muridarum-infected NK-depleted mice (NK−DC) exhibited a less mature phenotype compared with that of DC from the infected mice without NK depletion (NK+DC). NK−DC produced significantly lower levels of both IL-12 and IL-10 than those of NK+DC. Moreover, NK−DC showed reduced ability to direct primary and established Ag-specific Th1 CD4+ T cell responses in DC–T coculture systems. More importantly, adoptive transfer of NK−DC, in contrast to NK+DC, failed to induce type 1 protective immunity in recipients after challenge infection. Finally, NK cells showed strong direct enhancing effect on IL-12 production by DC in an NK–DC coculture system, which was partially reduced by blocking NKG2D receptors signaling and virtually abolished by neutralizing IFN-γ activity. The data demonstrate a critical role of NK cells in modulating DC function in an intracellular bacterial infection.

Section: Discussionsupporting

confidence: 71%

“…A line of evidence indicates that NK cells can regulate DC function and that NK-DC cross-regulation plays an important role in dictating the quality and the quantity of the adaptive immune responses (16)(17)(18)(19)(20)(21). A recent study showed that NK cells can enhance the capacity of DC to present parasitic Ags via the NKG2D receptor pathway (21).…”

mentioning

confidence: 99%

NK Cells Promote Type 1 T Cell Immunity through Modulating the Function of Dendritic Cells during Intracellular Bacterial Infection

Jiao

Gao

Joyee

et al. 2011

“…Investigators have shown that DCs and MFs require help from NK cells and NK cell-derived cytokines for maturation and proper functioning of APCs (39,40). A recent study has shown that DCs isolated from NK cell depleted mice could not be loaded with Ag and were incapable of activating memory specific lymphocytes (41). Cytokine production by these activated lymphocytes modulates other splenic populations, including DCs, MFs, neutrophils, and NK cells in control animals, which when might account for the significantly attenuated overall levels of IL-6 and IFN-g observed in immunized NK cell-depleted mice.…”

Section: Discussionmentioning

confidence: 99%

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

Hall

Clare

Dougan

2010

“…Therefore, NK cell recruitment due to activation by Ribi may be less extensive than that induced by the injection of DCs that have been activated in vitro (29). Furthermore, the interaction between DCs and NK cells can result in negative as well as positive sequelae (41)(42)(43). Clearly, however, mature NK cells are localized to the splenic red pulp (44 -46) where, upon activation, they are likely to encounter B cells in the marginal zone.…”

Section: Discussionmentioning

confidence: 99%

NK Cell Enhancement of Antigen Presentation by B Lymphocytes

Jennings

Yuan

2009

Ag presentation to CD4 T cells can be mediated by a number of cell types depending on the anatomical site in which Ag is first encountered. For blood borne Ags, cells localized in situ in the spleen should be major players. There is now much evidence that B cell Ag presentation may be particularly important in the priming of memory T cells. The majority of NK cells are also localized the spleen. Inasmuch as we have previously shown that NK cells can modulate various aspects of B cell differentiation, we entertained the possibility that NK cells can also influence Ag presentation by B cells. By specific depletion of NK cells before immunization, we show herein that NK cells play an important role in modulating the ability of B cells to process and present Ag to T cells. These effects are particularly important in the generation of memory T cells. The findings are further substantiated by in vitro experiments showing that the enhancement does not require IFN-γ but is mediated by direct cell-cell interaction. These results show, for the first time, that the rapid activation of a component of the innate response can even exert effects on the Ag-specific memory response.