Icam-1 is required for the early formation of granulomas and participates in the resistance of mice to the infection with...

• Grant number: 06/04164-4
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: October 01, 2006
• End date: March 31, 2007
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: João Santana da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The migration of leukocytes to inflammatory sites elicited by Paracoccidioides brasiliensis is supposed to be coordinated by cytokines and chemokines. Here, we investigated the role of ICAM-1 in the recruitment of inflammatory cells to lungs of mice infected with P. brasiliensis and in the outcome of the disease. We found that the expression of ICAM-1 was up-regulated on T lymphocytes after the infection with the fungus and that its expression is dependent on IFN-g, TNF-a, and IL-12. Moreover, the absence of ICAM-1 results in high susceptibility to the infection and delayed formation of granulomatous lesions. Also, the absence of ICAM-1 results in increased growth and dissemination of fungus, decreased number of CD3+CD4+ and CD3+CD8+ T cells, and increased production of IL-4 in the inflammatory site. The organization of a granulomatous reaction in mice deficient of ICAM-1 was delayed, starting only on day 60 after infection, while in WT mice it was complete on day 30 of infection. These data show that ICAM-1 is effectively involved in cellular migration and in the organization of the granulomatous lesion caused by the fungus P. brasiliensis. (AU)