Surface proteins of Setaria cervi induce inflammation in macrophage through Toll-like receptor 4 (TLR4)-mediated signalling pathway.

Lymphatic filariasis is a vectorborne parasitic disease that results in morbidities, disabilities and socio-economic loss each year globally. Inflammatory consequences associated with any form of filariasis have drawn special attention. However, the molecular insight behind the inflammation of host macrophage (MФ) is considered as one of the shaded areas in filarial research. Herein, major emphasis was given to study the signalling pathway of MФ inflammation induced by surface proteins (SPs) of filarial parasite through in vitro and in vivo approaches. Twenty-four hours of in vitro stimulation of Raw MФs with endotoxin-free SPs of Setaria cervi resulted in the secretion of pro-inflammatory cytokines (TNF-α and IL-1β) that revealed induction of inflammation, which was found to be elicited from classical NF-кB activation. Moreover, this NF-кB activation was found to be signalled from TLR4 and mediated by the downstream signalling intermediates, viz. MyD88, pTAK1 and NEMO. In vivo studies in adult Wistar rats, experimentally injected with SPs, clearly supported the outcomes of in vitro experiments by showing higher degree of inflammation rather classical activation of the peritoneal MФs. Therefore, SPs from S. cervi cuticle could be responsible for the induction of pro-inflammatory response in MФ, which appears to be propagated through TLR4-NF-кB route.