title: Resistance to Paracoccidioides brasiliensis infection is linked to a preferential Th1 immune response, whereas susceptibility is associated with absence of IFN-gamma production.
abstract: The secretion of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by antigen-stimulated lymph node cells, eosinophil maturation, and the antibody isotypes produced were examined during intraperitoneal infection of susceptible (B10.A) and resistant (A/Sn) mice with Paracoccidioides brasiliensis. Lymph node cells from resistant mice produced early and sustained levels of IFN-gamma and IL-2, whereas susceptible animals secreted low to undetectable amounts of these type 1 cytokines. Both mouse strains presented late and transient production of IL-4, whereas IL-10 was produced constantly throughout the course of disease. Resistant animals produced increasing levels of IL-5 in the chronic phase of the infection (from the eighth week on), whereas susceptible mice showed two peaks of IL-5 production, at the first and twelfth weeks after infection. Only the susceptible strain presented medullary and splenic eosinophilia concomitant with the raised IL-5 production. In resistant mice, the levels of IgG2a antibodies were significantly higher than those observed in susceptible mice, which preferentially secreted IgG2b and IgA isotypes. Taken together, these results demonstrate that a sustained production of IFN-gamma and IL-2 and a predominant secretion of IgG2a antibodies are associated with resistance to P. brasiliensis. In contrast, the production of low levels of IFN-gamma, early secretion of high levels of IL-5 and IL-10, eosinophilia, and a preferential secretion of IgG2b and IgA isotypes characterize the progressive disease in susceptible animals.
authors.affiliation: Depto. de Immunologia, Instituto de Ciências Biomédicas da Universitade de São Paulo, Brazil.
authors.forename: S S
authors.initials: SS
authors.lastname: Kashino
authors.forename: R A
authors.initials: RA
authors.lastname: Fazioli
authors.forename: C
authors.initials: C
authors.lastname: Cafalli-Favati
authors.forename: L H
authors.initials: LH
authors.lastname: Meloni-Bruneri
authors.forename: C A
authors.initials: CA
authors.lastname: Vaz
authors.forename: E
authors.initials: E
authors.lastname: Burger
authors.forename: L M
authors.initials: LM
authors.lastname: Singer
authors.forename: V L
authors.initials: VL
authors.lastname: Calich
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D051379:Mice; D008805:Mice, Inbred A; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007376:Interleukin-2; D015848:Interleukin-5; D007378:Interleukins; D007371:Interferon-gamma