title: Intercellular adhesion molecule-1 is required for the early formation of granulomas and participates in the resistance of mice to the infection with the fungus Paracoccidioides brasiliensis.
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 intercellular adhesion molecule-1 (ICAM-1) in recruiting inflammatory cells to lungs of mice infected with P. brasiliensis and in determining the outcome of the disease. Expression of ICAM-1 was up-regulated on T lymphocytes after infection with the fungus, and its expression was dependent on interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. Moreover, the absence of ICAM-1 resulted in high susceptibility to the infection and delayed formation of granulomatous lesions. In addition, the absence of ICAM-1 resulted in increased growth and dissemination of fungus, decreased number of CD3+CD4+ and CD3+CD8+ T cells, and increased production of interleukin-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, whereas in wild-type 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.
authors.affiliation: School of Medicine of Ribeirão Preto-USP, Department of Biochemistry and Immunology, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Moreira
authors.forename: Ana P
authors.initials: AP
authors.lastname: Campanelli
authors.forename: Karen A
authors.initials: KA
authors.lastname: Cavassani
authors.forename: Janeusa T
authors.initials: JT
authors.lastname: Souto
authors.forename: Beatriz R
authors.initials: BR
authors.lastname: Ferreira
authors.forename: Roberto
authors.initials: R
authors.lastname: Martinez
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Rossi
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D004198:Disease Susceptibility; D006099:Granuloma / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma