Inflammatory antigens of Brugia malayi and their effect on rodent host Mastomys coucha

Abstract

The study was aimed at identifying pro- and anti-inflammatory cytokine releasing potential of Brugia malayi adult worm fractions and their role in filarial infection and pathogenesis. THP-1 cells were incubated with soluble somatic Brugia malayi adult worm extract (BmAS) and its Sephadex G-200 fractions BmAFI, BmAFII and BmAFIII and the effect of the fractions on parasitological, immunological and lymph node parameters was assessed in Mastomys coucha. BmAFII stimulated the pro-inflammatory TNF-alpha, IL-1beta and IL-6 release; IL-10 release was insignificant. Sensitization of animals with BmAFII and subsequent intraperitoneal implantation of worms enhanced CMI response. BmAFII also increased lymph node weight and cellularity, stimulated lymph node mast cells and eliminated intraperitoneally instilled worms. BmAFI stimulated several folds more release of IL-10, whereas TNF-alpha release was negligible. Sensitization with BmAFI elicited low CMI responses, moderately stimulated mast cells and facilitated survival of implanted adult parasites. Fifty percent of naive animals exposed to BmAFI showed oedematous lymph nodes and increased node weight. NCP-bound molecules corresponding to BmAFI and II showed cytokine-stimulating potential in vitro. It is concluded that BmAFII is protective and stimulates pro-inflammatory cytokines, whereas BmAFI facilitates parasite survival and stimulates IL-10.

Recombinant Brugia malayi pepsin inhibitor (rBm33) induced monocyte function and absence of apoptotic cell death: An in vitro study

“…IFN-γ, bacterial products, and is produced by activated T cells [23]. Similar observations have been reported with THP-1 cell system using three stages of live parasites which showed microfilariae (mf) stimulated pro-inflammatory cytokine production more efficiently than third larval stage (L3) and adult stage of the parasites [24]. Besides this, the cytokine levels in rBm33 stimulated pooled culture supernatants showed difference in the gene and protein expression that could be attributed to post transcriptional, translational regulation and sensitivity of the assay.…”

Modulation of host’s immune responses and parasite load in Mastomys coucha immunized with recombinant mitochondrial HSP60 of human lymphatic filarial parasite Brugia malayi

“…Considerable degranulation, without any increase in mast cell number, was seen in the majority of lymph node mast cells of rmtHSP60bm-immunized animals receiving L 3 but not in non-immunized or non-immunized+L 3 infected animals. We have earlier reported similar absence of any significant numerical increase in lymph node mast cells after sensitization with anti-inflammatory BmAF1 fraction of adult worms (Dixit et al, 2004). This is not surprising because it is slowly becoming evident that mast cells can have both positive and negative immunomodulatory functions as seen in different mouse models of cutaneous hypersensitivity (Galli et al, 2005;Tsai et al, 2011) and in a mouse model of DTH to ovalbumin where impairment of antigen-specific T-cell responses were mediated by mast cells (Depinay et al, 2006).…”

Protective efficacy of a filarial surface antigen in experimental filariasis

“…A similar association has also observed in Brugian and Bancroftian filariasis, suggesting that antibodies to Mf sheath could be instrumental in eliminating circulating Mf (Ravindran et al , 2000). Several other filarial antigens with protective potential in animal models have been studied (Kazura et al , 1990; Dixit et al , 2004; Thirugnanam et al , 2007).…”