Neutrophils Reduce the Parasite Burden in Leishmania (Leishmania) amazonensis-Infected Macrophages

Background: Studies on the role of neutrophils in Leishmania infection were mainly performed with L. (L) major, whereas less information is available for L. (L) amazonensis. Previous results from our laboratory showed a large infiltrate of neutrophils in the site of infection in a mouse strain resistant to L. (L.) amazonensis (C3H/HePas). in contrast, the susceptible strain (BALB/c) displayed a predominance of macrophages harboring a high number of amastigotes and very few neutrophils. These findings led us to investigate the interaction of inflammatory neutrophils with L. (L.) amazonensis-infected macrophages in vitro.Methodology/Principal Findings: Mouse peritoneal macrophages infected with L. (L.) amazonensis were co-cultured with inflammatory neutrophils, and after four days, the infection was quantified microscopically. Data are representative of three experiments with similar results. the main findings were 1) intracellular parasites were efficiently destroyed in the co-cultures; 2) the leishmanicidal effect was similar when cells were obtained from mouse strains resistant (C3H/HePas) or susceptible (BALB/c) to L. (L.) amazonensis; 3) parasite destruction did not require contact between infected macrophages and neutrophils; 4) tumor necrosis factor alpha (TNF-alpha), neutrophil elastase and platelet activating factor (PAF) were involved with the leishmanicidal activity, and 5) destruction of the parasites did not depend on generation of oxygen or nitrogen radicals, indicating that parasite clearance did not involve the classical pathway of macrophage activation by TNF-alpha, as reported for other Leishmania species.Conclusions/Significance: the present results provide evidence that neutrophils in concert with macrophages play a previously unrecognized leishmanicidal effect on L. (L.) amazonensis. We believe these findings may help to understand the mechanisms involved in innate immunity in cutaneous infection by this Leishmania species.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of Scienc

In Vitro and In Vivo Activity of a Palladacycle Complex on Leishmania (Leishmania) amazonensis

Leishmaniasis is an important public health problem with an estimated annual incidence of 1.5 million of new human cases of cutaneous leishmaniasis and 500,000 of visceral leishmaniasis. Treatment of the diseases is limited by toxicity and parasite resistance to the drugs currently in use, validating the need to develop new leishmanicidal compounds. We evaluated the killing by the palladacycle complex DPPE 1.2 of Leishmania (Leishmania) amazonensis, an agent of human cutaneous leishmaniasis in the Amazon region, Brazil. DPPE 1.2 destroyed promastigotes of L. (L.) amazonensis in vitro at nanomolar concentrations, whereas intracellular amastigotes were killed at drug concentrations 10-fold less toxic than those displayed to macrophages. L. (L.) amazonensis-infected BALB/c mice treated by intralesional injection of DPPE 1.2 exhibited a significant decrease of foot lesion sizes and a 97% reduction of parasite burdens when compared to untreated controls. Additional experiments indicated the inhibition of the cathepsin B activity of L. (L.) amazonensis amastigotes by DPPE 1.2. Further studies are needed to explore the potential of DPPE 1.2 as an additional option for the chemotherapy of leishmaniasis