CELLULAR-REQUIREMENTS FOR IMMUNOMODULATORY EFFECTS CAUSED BY CELL-WALL COMPONENTS OF PARACOCCIDIOIDES-BRASILIENSIS ON ANTIBODY-PRODUCTION

In a previous study, we reported an increase in the number of immunogl obulin-secreting cells and the augmentation of antibody production (Ig M and IgG3) against unrelated antigens (sheep erythrocytes or bovine s erum albumin (BSA)) in mice infected with the fungus Paracoccidioides brasiliensis as well as in mice inoculated with its cell wall preparat ion (CW). The immunomodulatory effect of the live fungus and CW prepar ation was dose-dependent and mainly restricted to the i.p. inoculation simultaneously to the BSA challenge by the i.v. route. In the present study, we investigated the active component of CW preparation upon th e phenotype and also the degree of activation of possible target perit oneal cells involved in those phenomena. An insoluble polysaccharide f raction (F-1 fraction) mainly composed of beta-glucan and chitin, and the purified beta-glucan (BGPb) behaved as CW in the augmentation of e arly antibody production. The peritoneal mononuclear inflammatory cell s induced by CW, F-1 fraction and BGPb were highly positive to alpha-n aphthyl esterase staining; released low H2O2, expressed high levels of MHC-Ia(d) molecules and produced inflammatory cytokines such as tumou r necrosis factor-alpha (TNF-alpha) and IL-6. Phenotypic analysis by f low cytometry and immunohistochemical techniques of the inflammatory c ells responding to F-1 fraction showed a prevalence of (CD 11b/CD18, M ac-1)(+) peritoneal macrophages. In addition, s.c. inoculation of F-1 fraction resulted in the formation of nodular, localized and not progr essive granulomatous lesions with an accumulation of (CD11b/C18)(+) ma crophages. Adoptive transferred Mac-1 macrophages to immunized syngene ic recipient mice were able to cause an increase in anti-BSA antibody production. These results suggest that inflammatory (CD11b/CD18)(+) ma crophages may be related to immunological disturbances, caused by cell wall components of P. brasiliensis.