title: Cellular requirements for immunomodulatory effects caused by cell wall components of Paracoccidioides brasiliensis on antibody production.
abstract: In a previous study, we reported an increase in the number of immunoglobulin-secreting cells and the augmentation of antibody production (IgM and IgG3) against unrelated antigens (sheep erythrocytes or bovine serum albumin (BSA)) in mice infected with the fungus Paracoccidioides brasiliensis as well as in mice inoculated with its cell wall preparation (CW). The immunomodulatory effect of the live fungus and CW preparation 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 the phenotype and also the degree of activation of possible target peritoneal cells involved in those phenomena. An insoluble polysaccharide fraction (F1 fraction) mainly composed of beta-glucan and chitin, and the purified beta-glucan (BGPb) behaved as CW in the augmentation of early antibody production. The peritoneal mononuclear inflammatory cells induced by CW, F1 fraction and BGPb were highly positive to alpha-naphthyl esterase staining; released low H2O2; expressed high levels of MHC-Ia(d) molecules and produced inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-6. Phenotypic analysis by flow cytometry and immunohistochemical techniques of the inflammatory cells responding to F1 fraction showed a prevalence of (CD11b/CD18, Mac-1)+ peritoneal macrophages. In addition, s.c. inoculation of F1 fraction resulted in the formation of nodular, localized and not progressive granulomatous lesions with an accumulation of (CD11b/C18)+ macrophages. Adoptive transferred Mac-1 macrophages to immunized syngeneic recipient mice were able to cause an increase in anti-BSA antibody production. These results suggest that inflammatory (CD11b/CD18)+ macrophages may be related to immunological disturbances, caused by cell wall components of P. brasiliensis.
authors.affiliation: Department of Parasitology, Microbiology and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Silva
authors.forename: A L
authors.initials: AL
authors.lastname: Bocca
authors.forename: R
authors.initials: R
authors.lastname: Ferracini
authors.forename: F
authors.initials: F
authors.lastname: Figueiredo
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis*; D018821:CD18 Antigens / Q000276:immunology*; D002473:Cell Wall / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000378:metabolism; D006942:Hypergammaglobulinemia / Q000276:immunology; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D016177:Macrophage-1 Antigen / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology*
chemical_list: D000908:Antibodies, Fungal; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D006861:Hydrogen Peroxide