Immune responses to excretory/secretory antigens of Brugia malayi in the rhesus monkey (Macaca mulatta)
Description
The kinetics of cellular and humoral immune responses in rhesus monkeys (Macaca mulatta) to excretory/secretory (E/S) antigens of adult (Ad) worms of Brugia malayi were studied after experimental inoculation with B. malayi infective larvae (L3). The role of E/S antigens in modulating nonspecific immune responses was also investigated. Five rhesus monkeys were inoculated subcutaneously with 100 L3 in the lower legs. All five inoculated monkeys developed patent infections between 10-12 weeks postinfection (WPI). The blastogenic responsiveness of peripheral blood mononuclear cells (PBMCs) to E/S and Ad antigens, measured in vitro, increased by week 4 and decreased by week 12. The decrease coincided with the onset of patency in infected animals. The blastogenic responses to E/S antigens were, in general, lower than those o Ad antigens. The responses to mitogens (Con A and PWM) and to the unrelated antigen Candida albicans remained unchanged during the 24-week period of the study. No correlations were observed between antigen responses and microfilarial densities in infected animals. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) produced by E/S-and Ad-stimulated PBMCs correlated with the in vitro PBMCs blastogenic responses to these antigens. Parasite-specific IgG antibody responses detected by the ELISA were lower in response to E/S antigens compared to Ad antigens. Western blot analysis revealed that the intensity and number of bands recognized by antibodies in blots of E/S antigens were less and fewer, respectively, than those in blots of Ad antigens. Further investigations determined that PBMCs treated with E/S and subsequently co-cultured with freshly obtained syngeneic PBMCs in the presence of Con A produced a response to Con A that was 42% lower than cultures with cells lacking E/S treatment. E/S suppression was dose-dependent. An initial biochemical characterization of this E/S modulating molecule(s) showed that it is a protein. Flow cytometry studies showed no changes in CD8+ or CD4+ cell numbers or IL-2R expression on both cell types in Ad- or E/S- stimulated PBMCs cultures. This study has demonstrated that E/S antigens of B.malayi may play a role in modulating the immune responses in experimentally infected rhesus monkeys and thus, probably, in humans