Resistance to Paracoccidioides brasiliensis infection is linked to a preferential Th1 immune response, whereas susceptibility is associated with absence of IFN-gamma production

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 maturati on, and the antibody isotypes produced were examined during intraperitoneal infection of susceptible (B10.A) and resistant (A/Sn) mice with Paracoccid ioides brasiliensis. Lymph node cells from resistant mice produced early an d sustained levels of IFN-gamma and IL-2, whereas susceptible animals secre ted low to undetectable amounts of these type 1 cytokines, Both mouse strai ns presented late and transient production of IL-4, whereas IL-10 was produ ced 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 shelved two peaks of IL-5 product ion, at the first and twelfth weeks after infection. Only the susceptible s train presented medullary and splenic eosinophilia concomitant with the rai sed IL-5 production. In resistant mice, the levels of IgG2a antibodies were significantly higher than those observed in susceptible mice, which prefer entially secreted IgG2b and IgA isotypes, Taken together, these results dem onstrate that a sustained production of IFN-gamma and IL-2 and a predominan t secretion of IgG2a antibodies are associated with resistance to P. brasil iensis. In contrast, the production of low levels of IFN-gamma, early secre tion of high levels of IL-5 and IL-10, eosinophilia, and a preferential sec retion of IgG2b and IgA isotypes characterize the progressive disease in su sceptible animals.