Fig. 6.2.

The role of DCs in mucosal SIV transmission. SIV can cross the multilayered squamous epithelium of the ectocervix/vagina and the columnar epithelium of the endocervix and rectum. Cell-free or cell-associated SIV (not shown) is trapped in mucus covering the epithelium. At mucosal surfaces during SIV exposure, DCs are proposed to be among the first target cells to encounter virus. These DCs include LCs in the epithelium and immature mDCs in the submucosa. CLRs (CD207, CD209) or other attachment factors expressed on immature DCs are capable of binding SIV and transferring virus in trans to CD4⁺ T cells locally in the mucosa or in the LNs. SIV carrying DCs can mature as the result of infection or cytokines/chemokines present in the mucosa during infection. Virus crosses the mucosal barrier to establish small founder population that expands using outside-in signaling identified in the endocervix and resulting in endocervical CCL20 production, subsequent recruitment of CCR6⁺ pDCs, CCR5⁺ target cell expressing chemokines, and production of IFN-α. SIV also induces the production of TSLP by vaginal epithelial cells that leads to DC maturation and fueling of DC-mediated transmission. In the rectal mucosa CD209⁺ cells and CD4⁺ T cells are among the first targets of SIV. HSV-2 is one of the main cofactors for HIV infection. HSV-2 can infect mDCs and increase the susceptibility of mucosal CD4⁺ T cells to SIV infection by RA-mediated induction of α4β7 on the T cells, as it was demonstrated in vitro