Evaluation of macrophages and T cells activity in murine experimental models of high and low antibody-producers (selection IV-A) infected with Paracoccidioides brasiliensis

THESIS

Evaluation of macrophages and T cells activity in murine experimental models of high and low antibody-producers (selection IV-A) infected with Paracoccidioides brasiliensis

C. C. Pedigone

^{Correspondence}

THESIS. C. C. Pedigone submitted this thesis for her Masters in Tropical Diseases at Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil, 1998.

Advisor: Professor Sílvio Luis de Oliveira

ABSTRACT

The goal of this work was to evaluate the activity of macrophages and T cells in murine experimental models of paracoccidioidomycosis using High (H) and Low (L) antibody-producer mice of the IV-A selection, and to explain the differences in the pattern of pulmonary lesions showed by both strains. Animals were intravenously infected with 18 strains of P. brasiliensis (2.0 x 105 yeast/animal) and sacrificed after 3 days, and 1, 2, and 4 weeks. The following parameters were observed: recovery of viable fungi from pulmonary lesions; lymphocytes proliferative response to Concanavalin A (Con A); INF-g determination in the serum and in the supernatant of spleen cells culture; and H₂O₂, NO, and TNF-a release by peritoneal macrophages. H_IV-A mice had a higher recovery of viable fungi from the lung in the beginning of the infection (3 days and 1 week) when compared with L_IV-A. This was inverted in the last periods of time, and L_IV-A showed a higher recovery of fungi. With regards to the lymphocytes proliferative response, there was a positive association between the higher recovery of fungi in the H_IV-A strain and the lower proliferative response only after 3 days and 1 week. Higher levels of INF-g were remarkably related to lower recovery of fungi in the H_IV-A animals. With respect to the activation state of macrophages, the higher production of H₂O₂ in the H_IV-A strain after 3 days was associated to a control of the fungi multiplication in the lung. On the other hand, the decrease in this metabolite production in the L_IV-A strain was associated to an increase in the recovery of fungi. NO production was increased in H_IV-A strain when these animals showed lower recovery of fungi, but this association cannot be made in the L_IV-A. Another indicative of macrophage activation was TNF-a production. This cytokine level was high in the beginning of the infection in both strains. However, this increase cannot be associated to a possible control of fungi multiplication, mainly in the H_IV-A strain, when the increase of this cytokine was associated to a higher fungi recovery. Thus, the higher levels of TNF-a showed by the infected animals, when compared to controls, were considered as a parameter of macrophage activation and not as a regulatory cytokine involved in fungi multiplication. Our results show the important role of INF-g in the defense mechanisms against P. brasiliensis.

Key words:Paracoccidioides brasiliensis, Biozzi mice, immune response.

Publication Dates

• Publication in this collection
  21 Nov 2005
• Date of issue
  Dec 2005