Figure 10
Integrated model of the inter-dependent factors involved in dM differentiation and natural resistance to HIV-1 infection. In case of HIV-1 infection, p21 blocks HIV-1 replication at the reverse transcription and integration steps (1). In parallel, TLR7/8 activation by HIV-1 sequences (2) add an extra brake after the reverse transcription step and at or before the integration step (3). TLR7/8 triggering may also limit viral entry by inducing β-chemokine secretion (4) and by downregulating HIV-1 receptor and co-receptor expression (5). In addition, TLR7/8 triggering induces IFN-γ and TNF-α release from dNK cells (6), which favors an M1 switch of neighboring dM (7) and increases p21 expression (8). In parallel, TLR7/8 induce IL-1RA and IL-10 secretion that restrain TLR-induced inflammatory activation and tissue damage (9). In conclusion, the decidual pro/anti-inflammatory cytokine balance shape the phenotype of dM and their permissivity to HIV-1 infection (10). dM, decidual macrophages; dNK, decidual natural killer cells; IFN, interferon; TLR, Toll-like receptor; TNF, tumor necrosis factor.
