Definitional and characterisation of human tissue mononuclear phagocytes and their role in HIV transmission
Mononuclear phagocytes (MNP) consist of Langerhans cells, macrophages and dendritic cells (DC). They can become infected by HIV and transport the virus to its primary target cells (CD4 T cells) in association with their antigen presenting cell function.
We have revealed that the MNPs within anogenital tissues significantly differ to those in other parts of the body and we have defined three that preferentially transmit HIV; (i) epithelial cDC2, (ii) lamina propria langerin+ cDC2 and CD14+ monocyte derived DCs. We have also shown HIV causes MNP to form clusters with T cells within 2 hours of topical application and that the virus preferentially localises to DCs. Furthermore, DCs traffic HIV to lymphoid follicles which provide a conduit for the virus to enter the submucosa where it preferentially interacts with macrophages.
These observations significantly advance our understanding of HIV transmission by (i) defining the specific MNPs that capture and transmit HIV (ii) demonstrating that transfer of HIV by MNPs to CD4 T cells occurs within mucosal tissue within 2 hours (rather than lymph nodes) and (iii) that HIV is actively trafficked between mucosal tissue compartments. This is essential information for vaccine design and adds important data regarding early seeding of the viral reservoir.