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

Abstract

Recently we have shown that mitochondrial HSP60 of Brugia malayi (mtHSP60bm) shows high degree of homology with Escherichia coli GroEL/ES and that the ATP binding pockets of HSP60 in humans, E. coli and B. malayi were structurally conserved. In the present study we investigated the immune responses to rmtHSP60bm in Mastomys coucha and the fate of infection in the immunized animals. The animals received 4 immunization doses of rmtHSP60bm and were subsequently exposed to B. malayi infection. Microfilaremia, adult worm status, nitric oxide (NO), Th1 (IFN-g, IL-2) and Th2 (IL-4, IL 10 and TGF-β) cytokine release, cell proliferative response, levels of specific IgG and its subclasses, and the mast cell status in lymph nodes were assessed on day 135/136 post infection. Immunization with rmtHSP60bm and subsequent exposure to infection resulted in significantly high microfilaraemia but without any change in adult worm burden. Immunization with rmtHSP60bm increased IgG, IgG1 and IgG2b levels, and IL-2 and IFN-g release and suppressed NO release and CMI responses, but without any change in IL-4 and IL-10 release. Exposure of immunized animals to infection enhanced the CMI responses and, NO and IL- 10 release but decreased IgG1 levels and IL-2 and IL-4 release; however, IgG, IgG2a, IgG2b, and IFN-g responses remained unaltered. Mast cells in the draining lymph nodes of immunized-infected animals showed significant degranulation but without any increase in cell count. However, no pathology was found in the lymph nodes. These findings indicate that mtHSP60bm may modulate and balance the host’s immune responses to favor parasite survival without inducing any pathology.