Open AccessSND1 promotes Th1/17 immunity against chlamydial lung infection through enhancing dendritic cell function
Author(s) -
Xinting Wang,
Chunyan Zhang,
Shuhe Wang,
Rasheduzzaman Rashu,
Richard K. Thomas,
Jie Yang,
Xi Yang
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009295
Subject(s) - adoptive cell transfer , immune system , immunity , foxp3 , immunology , chlamydia , dendritic cell , t cell , microbiology and biotechnology , biology
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.