Exosomes are nanosized membrane microvesicles (30–100 nm) that have the capability to communicate intercellularly and transport cell components (i.e., miRNA, mRNA, proteins and DNA). Exosomes are found in nearly every cell type (i.e., mast cells, dendritic, tumor, and macrophages). There have been many studies that have shown the importance of exosome function as well as their unique packaging and targeting abilities. These characteristics make exosomes ideal candidates to act as biomarkers and therapeutics for disease. We will discuss the biogenesis, composition, and relationship of exosomes with non-viral microbial infections including gram-negative bacteria, gram-positive bacteria, Leishmania and Trypanosoma cruzi.

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This paper describes a new role for the cysteine-cysteine (CC) chemokines RANTES, MIP-1α, and MIP-1β on human macrophage function, which is the induction of nitric oxide (NO)-mediated trypanocidal activity. In a previous report, we showed that RANTES, MIP-1α and MIP-1β enhance Trypanosoma cruzi uptake and promote parasite killing by human macrophages (M. F. Lima, Y. Zhang, and F. Villalta, Cell. Mol. Biol. 43:1067–1076, 1997). Here we study the mechanism by which RANTES, MIP-1α, and MIP-1β activate human macrophages obtained from healthy individuals to kill T. cruzi. Treatment of human macrophages with different concentrations of RANTES, MIP-1α, and MIP-1β enhances T. cruzi trypomastigote phagocytosis in a dose peak response. The optimal response induced by the three CC chemokines is attained at 500 ng/ml. The macrophage trypanocidal activity induced by CC chemokines can be completely inhibited by l-N-monomethyl arginine (l-NMMA), a specific inhibitor of thel-arginine:NO pathway, but not by itsd-enantiomer. Culture supernatants of chemokine-treated human macrophages contain increased NO2 −levels, and NO2 − production is also specifically inhibited by l-NMMA. The amount of NO2 − induced by these chemokines in human macrophages is comparable to the amount of NO2 − induced by gamma interferon. The killing of trypomastigotes by NO in cell-free medium is blocked by an NO antagonist or a NO scavenger. This data supports the hypothesis that the CC chemokines RANTES, MIP-1α, and MIP-1β activate human macrophages to kill T. cruzi via NO, which is an effective trypanocidal mechanism.

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