Participation of the glycoprotein gp43 and B-1 cells on the genesis of the paracoccidioidomycotic granuloma

Abstract

The mechanisms which determine the infectious or non-infectious granulomata are still poorly known (Mariano, 1995). Among the animated and inanimate agents which induce a granulomatous response, the fungus Paracoccidioides brasiliensis must be considered with relevance. So, it is unquestionable that the better comprehension of the biological significance as well as the mechanisms which govern granuloma formation in paracoccidioidomycosis, should contribute to strategies of prophylactic and therapeutic control of this relevant endemia. In a recent publication, Kipnis (1998) has demonstrated that Xid mice are resistant to experimental infection with P. brasiliensis. Xid mice have a mutation in one aminoacid of the N-terminal portion of the Burton's tyrosine kinase enzyme. This molecular alteration is responsible for the X-linked agammaglobulinemia in man (XLA) and to the X-chromosome-linked B cell immunodeficiency in mice (Xid). Pre-B bone-marrow lymphocytes are found in normal numbers in these animals although the production of IgM and IgG immunoglobulins by these cells is very low and they do not respond to type-2 thymus-dependent antigens.(Narendran, et all, 1993; Snapper, et all, 1992). It is well established that peripheral B lymphocytes of Xid mice are immature and that the sub-populationB-1 cells is absent (Hardy & Hayakawa, 1994). Based on these informations, this project aims on the one hand to investigate the participation of the glycoprotein gp-43, the main antigenic component of the fungus Paracoccidioides brasiliensis, on the genesis of the granuloma formation in vitro and in vivo. On the other hand, the project aims also to investigate the participation of B-1 cells on the genesis and formation of the experimental paracoccidioidomicotic granuloma. To achieve these objectives, a model of granuloma formation in vitro will be developed. The evolvement of the fungal proteins, the immunologic cells and mechanisms and the participation of extra-cellular matrix components on the process will be evaluated. It will be also evaluated the participation of B-1 cells on the development of in vitro granuloma formation. B-1 cells will be obtained from cultures of normal mouse peritoneal cells, characterized and isolated by flow cytometry using cell surface markers. Preliminary results from this laboratory demonstrated that B-1 cells modulate themselves in vitro into mononuclear phagocytes (B-1 Derived Mononuclear Phagocyte - B-1 DMP) (Umpublished data). Thus, the participation of B-1 and B-1 DMP cells on inflammation, on granuloma formation in vitro and on the evolution of Paracoccidioides brasiliensis-induced granuloma in X-td mice - an animal deficient of B-1 cells -will be investigated. (AU)