Correlation among immune response, morphogenesis of the granulomatous reaction and spleen lymphoid structure in murine experimental paracoccidioidomycosis

We studied the correlation among cellular immune response, the pattern of l ung granulomatous lesions and alterations in spleen lymphoid structure in S wiss mice inoculated intravenously with Paracoccidioides brasiliensis strai n 18. The animals were evaluated at 24, 48 and 96 h after infection and fur ther studied weekly for 18 weeks by: (i) the macrophage migration inhibitio n test with phytohemagglutinin (PHA) and P. brasiliensis antigen (PbAg); an d (ii) histopathology of the lung and spleen lesions. One group of animals was gamma -irradiated (8 Gy), infected under the same conditions and evalua ted for the pattern of lung granulomatous lesions and spleen lymphoid struc ture at 24, 48 and 96 h after infection. During the first week of infection , the non-irradiated animals presented a positive response to PHA and PbAg, compact granulomas in the lungs and a typical hyperplasia of the spleen wh ite pulp. However, from weeks 2 to 5, a depression of the cell-mediated imm unity (CMI) response to PHA and PbAg was observed in association with granu lomas presenting only large mononuclear cells and lacking both giant cells and a peripheral halo of small mononuclear cells. This pattern of granuloma formation was similar to that seen in gamma -irradiated animals, whose cel ls involved in CMI were absent. After week 7, the non-irradiated animals sh owed granulomas characterized by the presence of giant cells and a peripher al halo of small mononuclear cells. This type of granuloma was formed conco mitantly with recovery of the CMI and of the lymphoid structure of the sple en. The results showed a correlation among granulomas composed of large mon onuclear cells, hypoplasia of the splenic tissue and impaired CMI. This cor relation indicated that although granuloma morphogenesis per se does not de pend on the activation of CMI, this response is important at later stages d uring modulation of the cellular composition of the granulomas.