Macrophages participate in host protection and the disease pathology associated with Leishmania braziliensisinfection

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.

Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-γ production by spleen cells from human visceral leishmaniasis patients

“…Although we did not show a direct role for TNF-α in killing of parasites, our results indicate immune modulatory effects of TNF-α during VL, especially in the spleen. Leishmania infected macrophages produces large amount of TNF-α [40] and this TNF-α can contribute to IFN-γ production by T cells and NK cells [41], so TNF-α blockade could interfere with IFN-γ secretion, as supported by our data. Neutralization of TNF-α has previously been reported to inhibit IFN-γ production by CD8 + T cells [42; 43], and we have also shown that CD8 + T cells contribute to endogenous IFN-γ production in SA cell cultures [44].…”

Protective and Pathological Functions of CD8+T Cells in Leishmania braziliensis Infection

“…We previously showed that while macrophages from both CL and ML patients exhibit predominantly proinflammatory profiles and secrete significantly more CXCL9, CXCL10, and TNF-␣ than do macrophages from SC subjects, macrophages from SC subjects have a greater ability to kill L. braziliensis than macrophages from CL or ML patients (37). For L. panamensis infection, others have shown that monocytes from SC individuals are less permissive to leishmania invasion or phagocytosis than monocytes from patients with relapsed episodes of CL (38).…”

Combining Cationic Liposomal Delivery with MPL-TDM for Cysteine Protease Cocktail Vaccination against Leishmania donovani : Evidence for Antigen Synergy and Protection

“…5B). However, no significant difference in amastigote killing activity was noted between rCPC and cocktail vaccinates after 72 h. This may be due to the reason that control of in vitro infection by MΦ is not solely due NO production but also by the milieu of cytokines and chemokines, specially IL-12 and TNF-α secreted by the parasitized APCs [53]. Almost comparable levels of these may also account for the lack of significant difference in parasite clearance between rCPC and cocktail vaccinates in vitro.…”