C5a and C5a(desArg) enhance the susceptibility of monocyte-derived macrophages to HIV infection

Mononuclear phagocytes, which include circulating blood monocytes and diffe rentiated tissue macrophages, are believed to play a central role in the se xual transmission of HIV infection. The ability of HIV to productively infe ct these cells may be influenced by action of exogenous or host-derived sub stances at the site of viral entry. Given the potent capacities of inflamma tory mediators to stimulate anaphylatoxic and immunomodulatory functions in mucosa, the effects of complement-derived anaphylatoxins on the susceptibi lity of monocytes and monocyte-derived macrophages (MDM) to HIV-1 infection were examined. In our in vitro system, the susceptibility to infection was up to 40 times increased in MDM that had been exposed to C5a or C5a(desArg ), but not to C3a or C3a(desArg), for 2 days before adding of virus. By con trast, the treatment with complement anaphylatoxins did not affect HIV repl ication in fresh monocytes. Stimulatory effect of C5a and its desArg deriva tive on HIV infection correlated with the increase of TNF-alpha and IL-6 se cretion from MDM. All these functional effects of C5a and C5a(desArg) were reversible by treatment of cells with the mAb that functionally blocks C5aR , Taken together, these results indicate that C5a and C5a(desArg) may incre ase the susceptibility of MDM to HIV infection through stimulation of TNF-a lpha and IL-6 secretion from these cells.