Nitric oxide participation in granulomatous response induced by Paracoccidioides brasiliensis infection in mice.
The role of nitric oxide (NO) in granulomas of Paracoccidioides brasiliensis-infected inducible NO synthase-deficient C57BL/6 mice (iNOS KO) and their wild-type counterparts and its association with osteopontin (OPN) and matrix metalloproteinases (MMPs) was studied. At 15 days after infection (DAI), iNOS KO mice showed compact and necrotic granulomas with OPN+ macrophages and multinucleated giant cells, whereas wild-type mice developed loose granulomas with many fungi and OPN+ cells distributed throughout the tissue. In addition, high OPN levels and fungal load were observed in iNOS KO mice. Both experimental groups had MMP-9 activity. At 120 DAI, iNOS KO had smaller granulomas with OPN+ cells, lower OPN levels, lower fungal load and decreased MMP-9 activity compared with wild-type mice. These findings suggest that NO has an important role in granuloma modulation, by controlling OPN and MMP production, as well as by inducing loose granulomas formation and fungal dissemination, resulting, at later phases, in progression of paracoccidioidomycosis.
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes, 1730, Cidade Universitária, São Paulo 05508-900, Brazil.
Angela Satie
AS
Nishikaku
Raphael Fagnani Sanchez
RF
Molina
Luciana Cristina
LC
Ribeiro
Renata
R
Scavone
Bernardo Paulo
BP
Albe
Cláudia Silva
CS
Cunha
Eva
E
Burger
D000818:Animals; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D020778:Matrix Metalloproteinase 2 / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D009852:Omentum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D053495:Osteopontin / Q000276:immunology; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000382:microbiology
D053495:Osteopontin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse