The role of complement in the early phase of Leishmania (Leishmania) amazonensis infection in BALB/c mice

Abstract

Complement-depleted and -non-depleted BALB/c mice were inoculated with Leishmania (Leishmania) amazonensis promastigotes into the hind footpad to study the role of the complement system in cutaneous leishmaniasis. Total serum complement activity was measured by hemolytic assay and C3 fragment deposit at the inoculation site was determined by direct immunofluorescence in the early period of infection, i.e., at 3, 24, 48 h and 7 days post-infection. The inflammatory reaction and the parasite burden were evaluated in the skin lesion at 7 and 30 days post-infection. Total serum complement activity decreased in the early phase of infection, from 3 to 24 h, in non-depleted mice compared to non-infected and non-depleted mice. C3 fragment deposit at the site of parasite inoculation was present throughout the period of infection in non-depleted mice. In contrast, no C3 fragment deposit was observed at the inoculation site in complement-depleted mice. Complement-depleted mice showed a significant decrease in the inflammatory response and a significant increase in the number of parasites (70.0 ± 5.3 vs 5.3 ± 1.5) at 7 days of infection (P < 0.05). A higher number of parasites were also present at 30 days of infection at the inoculation site of complement-depleted mice (78.5 ± 24.9 vs 6.3 ± 5.7). These experiments indicate that complement has an important role at the beginning of experimental cutaneous leishmaniasis caused by L. (L.) amazonensis by controlling the number of parasites in the lesion.

Dynamic High-Content Imaging Reveals Surface Exposure of Virulent Leishmania Amastigotes in Infected Macrophages Undergoing Pyroptosis

“…Consequently, in vivo , parasite trapping to pyroptotic debris may favor parasite spreading - as shown for other forms of host cell death – allowing for stealthy phagocytosis by freshly recruited macrophages in the inflammatory infection site (de Menezes et al, 2016). On the other hand, the extracellular exposure of amastigotes could expose parasites to complement-dependent cytotoxicity that is known to control parasite load in vivo (Laurenti et al, 2004), or to anti-leishmanial antibodies that could promote cell-mediated cytotoxicity via Fc receptor-dependent phagocytosis. Our results will stimulate future studies designed to assess the role of macrophage pyroptosis in Leishmania dissemination, transmission, and immune-pathology.…”

Innate immunity againstLeishmaniainfections

“…While in vivo study of C5‐deficient mice showed no role for complement in controlling L . major infection in vivo (Spath et al ., 2003a), a separate study that depleted the whole complement system in BALB/c mice using cobra‐venom anti‐complement protein challenge showed a profound role for complement in controlling L. amazonensis infection in vivo (Laurenti et al ., ). Thus, comprehensive in vivo studies with Leishmania infections of mice lacking individual components of complement (C3b –/– , C5b –/– , C5a –/– etc.)…”

Modulation of inflammation response to murine cutaneous Leishmaniosis by homeopathic medicines: Thymulin 5cH

“…14 We applied the same model to study the effect of thymulin 5cH in a parasitic experimental model, using Leishmania (L.) amazonensis infection. The idea to perform this study is based on the fact that this parasite causes very particular mechanisms of interaction with its host, modifying both natural and acquired immune responses, [14][15][16] including the phagocyte activity in the destruction of amastigote forms. 16,17 The aim of this study is to analyze the putative immune modulation mechanisms of thymulin 5cH treatment in the experimental infection with Leishmania (L.) amazonensis in mice, by using specific markers to recognize some immune cells involved in the local and systemic hostparasite interactions.…”