Granuloma formation around Brugia Larvae triggered by host responses to an E/S antigen
Schultz, Leonard D.
PublisherAmerican Society for Microbiology
MetadataShow full item record
In previous studies using a murine model of Brugia malayi infection, granuloma formation was found to be a most important host protective mechanism. Previous studies also showed that in vitro cytoadherence is a surrogate for the formation of anti-filarial granulomas in vivo and this function requires “alternatively activated” host cells and a source of anti-filarial antibody. In this manuscript we show that antibodies against L3 excretory/ secretory (E/S) products can facilitate in vitro cytoadherence. We generated a set of hybridomas reactive with filarial E/S products and screened them for their ability to mediate in vitro cytoadherence. One clone (1E9) that produced high titer of IgM antibodies were used in subsequent assays. To identify the antigen(s) recognized by the IE9 clone, we screened a T7 bacteriophage displayed cDNA expression library of B. malayi L3 with IE9 clone as the bait. . The screening procedure identified two filarial antigens (TCTP and BmALT-2) that bound to 1E9. Immunization of mice showed that the cohort immunized with BmALT-2 cleared a challenge infection with infective B. malayi L3 in an accelerated manner, whereas cohorts immunized with TCTP cleared larvae with the same kinetics as unimmunized mice. These data confirm that the antigenic target of granuloma-mediated killing of B. malayi L3 is possibly BmALT-2. Our findings also confirm previous studies that BmALT-2 is a potential vaccine candidate for filarial infection. Our data reinforce the work of others, and also provide a possible mechanism by which immune responses to BmALT-2 provide host protection.