The overall goal is to extend our knowledge about host defense against filarial infection. The work we are proposing for the upcoming period is based on the following central hypothesis: Host defense against Brugia infection is mediated by the formation of granulomas around infectious larvae. Over the past two years, we have focused particularly on the initiation of granuloma formation, with the discovery of some aspects of this reaction that were unanticipated by us. The current proposal seeks to extend these data. For all specific aims, we will use the in vivo intra-peritoneal model that we have employed over the past decade, in combination with the in vitro cytoadherence assay that we have refined over the ? past 2-3 years.
Specific Aim No. 1 seeks to address the hypothesis that antigen specific IgM is critical in host defense.
Specific Aim No. 2 addresses the hypothesis that the receptor on the PECs that binds to antigen specific IgM is the polymeric Ig receptor (hereafter plgR.) Specific Aim No. 3 will address the hypothesis that carbohydrate antigens on the cuticle are the epitopes that react with antigen-specific IgM. We believe that these experiments will extend our increasing understanding of the nature of host defense against filarial parasite. More excitingly, they might help us identify the epitope that forms the target of host defense raising the possibility, long-term, of generating an immuno-prophylactic strategy against filarial infections. ? ? ?
