Article
In situ characterization of the granulomatous immune response with time in nonhealing lesional skin of Leishmania braziliensis-infected rhesus macaques (Macaca mulatta)
Registro en:
LEMOS, Camila Souza; et al. In situ characterization of the granulomatous immune response with time in nonhealing lesional skin of Leishmania braziliensis-infected rhesus macaques (Macaca mulatta). Veterinary Immunology and Immunopathology, v.142, p.147– 155, 2011.
0165-2427
10.1016/j.vetimm.2011.05.002
1873-2534
Autor
Lemos, Camila Souza
Campos, Simone Neves de
Teva, Antonio
Porrozzi, Renato
Grimaldi Junior, Gabriel
Resumen
We have recently introduced a macaque (Macaca mulatta) model of Leishmania braziliensis-induced self-healing cutaneous leishmaniasis in which the T cell-mediated inflammatory response effectively promotes parasite clearance and granuloma resolution. Here we show that macaques infected with a highly pathogenic L. braziliensis strain displayed longstanding granulomatous lesions which lasted until the end of the observation period (52 weeks). Immunoperoxidase staining of representative tissue sections indicated that distinct cell populations (CD3, CD4, CD8, CD20, Foxp3, CD20, CD68, HLA-DR, CCL2, and CXCL-10) change uniformly during infection, suggesting that the same components of the local immune response are working in unison. This model also confirmed that granuloma formation is orchestrated by diverse inflammatory mediators that are important for T helper type 1 (Th1) cell development and macrophage effector functions. Cytometry analysis of ex vivo granuloma-derived leukocytes revealed accumulation of distinct functional subsets of effector and regulatory T cells into the inflamed skin. We provide evidence that local interleukin (IL)-10 production by both Foxp3(+) and Foxp3(-) CD4(+) T subsets is likely important in promoting lesional granuloma maintenance. Further studying the immune suppression mechanisms that induces granulomas in L. braziliensis-infected macaques may reveal new opportunities for therapeutic control of this important human disease. 2030-01-01