BETA-CHEMOKINES THAT INHIBIT HIV-1 INFECTION OF HUMAN MACROPHAGES STIMULATE UPTAKE AND PROMOTE DESTRUCTION OF TRYPANOSOMA-CRUZI BY HUMAN MACROPHAGES

Recently beta-chemokines have been shown to inhibit HIV-I infection of human macrophages. Here, we show that the beta-chemokines RANTES, MIP -1 alpha and MIP-1 beta enhance the uptake and cause intracellular des truction of Trypanosoma cruzi trypomastigotes by human macrophages obt ained from healthy individuals. The trypanosome enhancing uptake and t he trypanocidal effect induced by these beta-chemokines in human macro phages are abrogated by neutralizing antibodies to RANTES, MIP-1 alpha and MIP-beta, whereas irrelevant antibodies of the same class do not affect these parameters. These results indicate that the effects seen are beta-chemokine specific. Pretreatment of human macrophages with RA NTES, MLP-1 alpha and MIP-1 beta induced strong tyrosine phosphorylati on of several proteins, suggesting that signal transduction events are involved in enhanced trypanosome uptake and parasite killing. Taken t ogether these results suggest that the beta-chemokines RANTES, MIP-1 a lpha and MIP-1 beta, might pla-a beneficial role in parasite clearance and destruction in individuals infected with cruzi. Alternatively, th ese three beta-chemokines may play a beneficial role in individuals co ncurrently infected with 1 cruzi and HIV-1.