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Abstract
BackgroundLeishmania preferentially infects macrophages, which allow the parasite to multiply but can also kill the parasite. Although the T cell response in human leishmaniasis is well-characterized, little is known about the concomitant macrophage behavior. The aim of this study was to characterize the macrophage immune response after Leishmania braziliensis infection in cells derived from cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML) patients, subclinical individuals (SC) and healthy control subjects (HS).MethodsPeripheral blood mononuclear cell-derived macrophages from the different groups were exposed to L. braziliensis in vitro and were evaluated for susceptibility to Leishmania infection, ability to kill Leishmania and chemokine/cytokine production. Nitric Oxide (NO) and superoxide (O2-) levels in the supernatant of infected macrophage cultures were monitored.ResultsAfter exposure to L. braziliensis, peripheral blood mononuclear cell-derived macrophages from SC individuals showed a lower infection rate and a smaller number of intracellular amastigotes compared to cells from CL and ML patients. Macrophages from CL and ML patients produced more chemokines and TNF-α than those from the SC group. Production of NO and O2- were detected but did not vary significantly among the different groups.ConclusionsOur data indicate that macrophages play a pivotal role in controlling L. braziliensis infection and in leishmaniasis pathology by secreting pro-inflammatory chemokines/cytokines that activate and recruit T cells, overwhelming the inflammatory response.
Highlights
Leishmania preferentially infects macrophages, which allow the parasite to multiply but can kill the parasite
Susceptibility of human macrophages to L. braziliensis infection To determine the susceptibility of macrophages to L. braziliensis, as well as their ability to kill this parasite, adherent cells from the 4 different groups of subjects (HS, subclinical individuals (SC), cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML)) were infected with L. braziliensis stationary phase promastigotes
After 48 h, SC macrophages had a lower proportion of infected cells and a lower number of amastigotes per 100 cells compared to healthy control subjects (HS), CL and ML macrophages (SC × HS, p < 0.001; SC × CL, p < 0.01; SC × ML, p < 0.001)
Summary
Leishmania preferentially infects macrophages, which allow the parasite to multiply but can kill the parasite. The T cell response in human leishmaniasis is well-characterized, little is known about the concomitant macrophage behavior. The aim of this study was to characterize the macrophage immune response after Leishmania braziliensis infection in cells derived from cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML) patients, subclinical individuals (SC) and healthy control subjects (HS). CCL2 and CCL3 are known to increase the leishmanicidal ability of human macrophages to the same level induced by IFN-g [12]. Molecules such CXCL9, CXCL10 and TNF-a, which are highly expressed in the tissue from CL and ML patients, participate in the inflammatory reaction that may lead to the tissue damage observed in CL and ML [11,13]
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