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-1 infection of human macrophages. Here, we show that the beta-chemokines RANTES, MIP-1alpha and MIP-1beta enhance the uptake and cause intracellular destruction of Trypanosoma cruzi trypomastigotes by human macrophages obtained from healthy individuals. The trypanosome enhancing uptake and the trypanocidal effect induced by these beta-chemokines in human macrophages are abrogated by neutralizing antibodies to RANTES, MIP-1alpha 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 RANTES, MIP-1alpha and MIP-1beta induced strong tyrosine phosphorylation of several proteins, suggesting that signal transduction events are involved in enhanced trypanosome uptake and parasite killing. Taken together these results suggest that the beta-chemokines RANTES, MIP-1alpha and MIP-1beta, might play a beneficial role in parasite clearance and destruction in individuals infected with T. cruzi. Alternatively, these three beta-chemokines may play a beneficial role in individuals concurrently infected with T. cruzi and HIV-1.
Lima
M F
MF
Department of Microbiology, School of Medicine, Meharry Medical College, Nashville, Tennessee 37208, USA.
Zhang
Y
Y
Villalta
F
F
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology* / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000469:parasitology; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D019380:Anti-HIV Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D014443:Tyrosine