Snd1 Promotes Th1/17 Immunity Against Chlamydial Lung Infection Through Enhancing Dendritic Cell Function

To date, no reports have linked the multifunctional protein, staphylococcal nuclease domain-containing protein 1 (SND1), to host defense against intracellular infections. In this study, we investigated the role and mechanisms of SND1, by using SND1 knockout (SND1(-/-)) mice, in host defense against the lung infection of Chlamydia muridarum, an obligate intracellular bacterium. Our data showed that SND1(-/-) mice exhibited significantly greater body weight loss, higher organism growth, and more severe pathological changes compared with wild-type mice following the infection. Further analysis showed significantly reduced Chlamydia-specific Th1/17 immune responses in SND1(-/-) mice after infection. Interestingly, the dendritic cells (DCs) isolated from SND1(-/-) mice showed lower costimulatory molecules expression and IL-12 production, but higher IL-10 production compared with those from wild-type control mice. In the DC-T cell co-culture system, DCs isolated from SND1(-/-) infected mice showed significantly reduced ability to promote Chlamydia-specific IFN-gamma producing Th1 cells but enhanced capacity to induce CD4(+)T cells into Foxp3(+) Treg cells. Adoptive transfer of DCs isolated from SND1(-/-) mice, unlike those from wild-type control mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that SND1 plays an important role in host defense against intracellular bacterial infection, and suggest that SND1 can promote Th1/17 immunity and inhibit the expansion of Treg cells through modulation of the function of DCs.Author summarySince the initial study from our group reported that SND1 is able to hijack nascent MHC-I heavy chain in tumor cells, thereby impairing the proper assembling of MHC-I and sensitizing tumor cells to a diminished immune surveillance with abolished antigen presentation to cytotoxic CD8+ T cells, large attention has been drawn to its importance in host immunity. To date, no reports have been linked SND1 to immune response against bacterial infection. In this study, we investigated the role and mechanisms of SND1 in chlamydial lung infection by using SND1 knockout mice. We found that SND1 knockout mice showed significantly delayed clearance of bacteria and more severe disease. More importantly, we found that the SND1 deficiency led to alteration of phenotype and function of dendritic cells, which is associated with a failure in the development of protective Th1/17 immunity. These data indicate that SND1 protein plays an important role in host defense against chlamydial infection, at least partially through modulating dendritic cell function.