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

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.

Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections

“…For example, we recently found NK cells can influence macrophage polarization in the lung following chlamydial infection (71). Similarly, the newly reported molecules such as SND1 and Sema3E, which modulate DC functions in infections (72,73), would be an area for exploring the molecular mechanisms related to the modulating effect of NKT and NK cells on DC function infections. The data suggest the complexity of multiple innate and adaptive immune cell interaction levels in infections.…”

CPT-11 mitigates autoimmune diseases by suppressing effector T cells without affecting long-term anti-tumor immunity

“…4a, b ), and the proteins encoded by these genes have been shown to promote cell proliferation [ 26 – 32 ]. Interestingly, studies have suggested that SND1 and TXNIP play important roles in Th1 or Th17 cell-mediated immune responses [ 33 , 34 ]. These two genes were also down-regulated in CPT-11-treated CD4 + T cells (Fig.…”

The role of the 47-kDa membrane lipoprotein of Treponema pallidum in promoting maturation of peripheral blood monocyte-derived dendritic cells without enhancing C-C chemokine receptor type 7-mediated dendritic cell migration

“…This result is consistent with previously reported studies on DCs in most pathogenic infections. [36][37][38] After DCs uptake and process antigens, they undergo phenotypic and functional changes and gradually differentiate into mature DCs, which can provide the 2 nd signal necessary for T-cell activation. 39,40 Immune cell migration serves as a key link between immune regulation and host defense.…”