SND1 promotes Th1/17 immunity against chlamydial lung infection through enhancing dendritic cell function.

Xinting Wang,Jie Yang,Rony Thomas,Chunyan Zhang,Xi Yang,Shuhe Wang,Rasheduzzaman Rashu,Renée M Tsolis

doi:10.1371/journal.ppat.1009295

Xinting Wang, Jie Yang + Show 6 more

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https://doi.org/10.1371/journal.ppat.1009295

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Abstract

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-γ 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.

Highlights

Chlamydia trachomatis, an obligate intracellular bacterium, afflicts people with a broad range of diseases, including sexually transmitted diseases and pneumonia[1]
Since the initial study from our group reported that staphylococcal nuclease domain-containing protein 1 (SND1) is able to hijack nascent MHCI 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
We investigated the role and mechanisms of SND1 in chlamydial lung infection by using SND1 knockout mice

Summary

Introduction

An obligate intracellular bacterium, afflicts people with a broad range of diseases, including sexually transmitted diseases and pneumonia[1]. DCs are the primary antigen-presentation cells (APCs) of the immune system and have a key role in both sensing pathogens and tuning the immune responses[8,9]. They consist of various subtypes and are classified on the basis of their phenotype, location, and function[10,11]. Conventional DCs (cDCs) mainly reside in the lymphoid tissues such as thymus, spleen, and secondary lymph nodes (LNs) These conventional DCs exhibit higher levels of MHC-II and CD11c and can be subsequently divided into CD8α+ and CD8α− DCs in mice. CD103+ DC in the nonlymphoid organs such as gut, lung, and skin form a combined subset, which is developmentally related to the CD8+ cDC in lymphoid organs[13,15,16]

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