title: Osteopontin involvement in granuloma formation and in the severity of Paracoccidioides brasiliensis infection.
abstract: The participation of osteopontin (OPN) in Paracoccidioides brasiliensis infected mice, its association to granulomatogenesis, severity of infection, pattern of lesions, nitric oxide (NO) levels and fungal load were evaluated in this investigation. Immunohistochemistry analysis showed marked OPN staining in extracellular matrix and in macrophages and multinucleated giant cells at the center of lesions, suggesting a possible role of OPN in the distribution of these cells within the granulomas. At 15 days post-infection with a virulent P. brasiliensis isolate, OPN+ cells were more numerous and intensely immunostained in the loose granulomas of susceptible mice than in those of resistant mice. In addition, high fungal loads and low NO levels were observed in susceptible mice. At 120 days after infection, resistant mice had increased total OPN levels (ELISA) and OPN positivity in compact granulomas, higher NO levels and lower fungal loads than susceptible mice. Residual lesions associated with low OPN levels, high NO and control of fungal dissemination were observed in both mouse strains at 120 days post-infection with the slightly virulent fungal isolate. Therefore, OPN could be associated with higher severity of the disease in an early phase of infection and with a degree of control of the progressive infection.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Cidade Universitária, São Paulo-SP, Brazil.
authors.forename: Angela Satie
authors.initials: AS
authors.lastname: Nishikaku
authors.forename: Renata
authors.initials: R
authors.lastname: Scavone
authors.forename: Raphael Fagnani Sanchez
authors.initials: RF
authors.lastname: Molina
authors.forename: Bernardo Paulo
authors.initials: BP
authors.lastname: Albe
authors.forename: Cláudia Da Silva
authors.initials: Cda S
authors.lastname: Cunha
authors.forename: Eva
authors.initials: E
authors.lastname: Burger
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000378:metabolism* / Q000382:microbiology; D007150:Immunohistochemistry; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009852:Omentum / Q000737:chemistry; D053495:Osteopontin / Q000032:analysis / Q000378:metabolism*; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D053495:Osteopontin; D009569:Nitric Oxide