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.
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.
Moreira
Ana P
AP
School of Medicine of Ribeirão Preto-USP, Department of Biochemistry and Immunology, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brazil.
Campanelli
Ana P
AP
Cavassani
Karen A
KA
Souto
Janeusa T
JT
Ferreira
Beatriz R
BR
Martinez
Roberto
R
Rossi
Marcos A
MA
Silva
João S
JS
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
D015703:Antigens, CD; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma