Exploring the homolog of a novel proinflammatory microfilarial sheath protein (MfP) of Wuchereria bancrofti in the adult-stage bovine filarial parasite Setaria cervi

Abstract

A novel microfilarial sheath protein (MfP) of the human filarial parasite Wuchereria bancrofti and its proinflammatory activity on host macrophages were identified recently. MfP is a homolog of the nematode bestrophin-9 superfamily that acts as a ligand of macrophage Toll-like receptor 4 (TLR4) to induce inflammation through NF-κB activation. Therefore, the presence and functional implication of this novel protein in adult-stage parasites were open questions to answer. In this study, the bovine filarial parasite Setaria cervi was used to simulate adult W. bancrofti. We detected the presence of MfP in adult-stage S. cervi through clear immunological cross-reactivity and immunolocalization employing an anti-MfP antibody developed in mice. Therefore, our findings put forward S. cervi as a cost-effective source of immunodominant filarial antigen MfP to simulate its future utilization in the immunotherapeutic intervention of lymphatic filariasis.

Therapeutic Efficacy of Anti-Bestrophin Antibodies against Experimental Filariasis: Immunological, Immune-Informatics and Immune Simulation Investigations

“…Microfilariae of W. bancrofti were obtained from the filaria-endemic villages of Bankura, West Bengal following the procedure described in Mukherjee et al, 2017 [ 7 ]. On the other hand, the model filarial parasite S. cervi was obtained from the local abattoirs located in Asansol, West Bengal as per the protocol of Mukherjee et al, 2020 [ 8 ]. The adult female parasites were dissected and microfilariae were obtained [ 8 ].…”

“…On the other hand, the model filarial parasite S. cervi was obtained from the local abattoirs located in Asansol, West Bengal as per the protocol of Mukherjee et al, 2020 [ 8 ]. The adult female parasites were dissected and microfilariae were obtained [ 8 ].…”

“…In this context, a novel surface protein, namely FSAg/MfP, belonging to the nematode-bestrophin superfamily, was reported to be one of the crucial inducers of inflammatory consequences associated with bancroftian filariasis [ 7 ]. This protein is present in the cuticle of the filarid across all the developmental stages of the parasite [ 8 ]. FSAg acts a ligand for TLR4 located on the surface of human antigen presenting cells like macrophages and dendritic cells [ 6 , 7 ].…”

A review on the interactions between dendritic cells, filarial parasite and parasite‐derived molecules in regulating the host immune responses

“…Filarial parasites communicate with the host immune cells through several mechanisms, and the excretory‐secretory (ES) molecules (e.g. ES‐62) are one such resulting in activation of host immune cells 5,14‐16 …”

“…Since the last few decades, the therapeutic potentials of these TLRs are widely accepted in case of various parasitic infections 18 . Recently, a parasite‐derived molecule known as filarial sheath antigen (FSAg) has been reported to interact with the TLR4 on host DCs 14‐16,19 …”