A Novel Ligand of Toll-like Receptor 4 From the Sheath of Wuchereria bancrofti Microfilaria Induces Proinflammatory Response in Macrophages

Abstract

Microfilarial protein appears to be a new ligand of TLR4 from W. bancrofti. Determination of its functional attributions in the host-parasite relationship, especially immunopathogenesis of filarial infection, may improve our understanding.

Wuchereria bancrofti filaria activates human dendritic cells and polarizes T helper 1 and regulatory T cells via toll-like receptor 4

“…Dendritic cells were differentiated from peripheral blood monocytes of healthy donors of a non-endemic country (France). Our previous report has shown that microfilarial sheath antigen induces proinflammatory responses in macrophages 13 . Based on this previous study, initial experiments were performed with three concentrations (5, 10 and 25 μg) of microfilarial sheath antigen and found that even at 5μg concentration, sheath antigen could induce maturation-associated markers on dendritic cells and was used for all subsequent experiments.…”

“…However, despite responsible for 90% of the filaria infection in population, the interaction of W. bancrofti with dendritic cells and subsequent CD4 + T cell responses remain unexplored. Sheath antigen (~70 kDa) is an immunodominant antigen of W. bancrofti and is critical for inflammatory pathology associated with lymphatic filariasis 13 . Our previous investigation has revealed that microfilarial sheath antigen acts as a ligand for Toll-Like Receptor 4 (TLR4) and induces inflammation in macrophages through NF-κB activation 13 .…”

“…Sheath antigen (~70 kDa) is an immunodominant antigen of W. bancrofti and is critical for inflammatory pathology associated with lymphatic filariasis 13 . Our previous investigation has revealed that microfilarial sheath antigen acts as a ligand for Toll-Like Receptor 4 (TLR4) and induces inflammation in macrophages through NF-κB activation 13 . Intriguingly, antibody-mediated blockade of this protein abrogated filarial parasite-induced inflammatory responses in macrophages 13 .…”

“…Our previous investigation has revealed that microfilarial sheath antigen acts as a ligand for Toll-Like Receptor 4 (TLR4) and induces inflammation in macrophages through NF-κB activation 13 . Intriguingly, antibody-mediated blockade of this protein abrogated filarial parasite-induced inflammatory responses in macrophages 13 . In addition to microfilariae, sheath antigen is also present in adult filarid and responsible for the inflammatory consequences induced by the adult stage parasites 14 .…”

Quinolone-fused cyclic sulfonamide as a novel benign antifilarial agent

“…For in vitro toxicity evaluation, 1 × 10 6 mouse macrophages (RAW 264.7, ATCC, USA) were cultured in six well plates (Nest Biotechnology) with incomplete media (DMEM) containing 100 U/ml penicillin and 100 μg/ml streptomycin at 37 ο C in 5% CO 2 atmosphere following Mukherjee et al . 36 . Cells were treated with different concentrations (450 and 900 μM) of 8l for 24 hr.…”