Osteopontin involvement in granuloma formation and in the severity ofParacoccidioides brasiliensisinfection

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.

Novel Murine Model of Chronic Granulomatous Lung Inflammation Elicited by Carbon Nanotubes

“…However, regardless of etiology, common mechanisms are involved in the formation of granulomas. A series of complex, coordinated events brings about the recruitment of macrophages, T cells, cytokine release, and subsequent transformation of macrophages into epithelioid and multinucleated giant cells (17,20,(29)(30)(31)(32). Previous studies administered single and multiwall carbon nanotubes, and reported inflammatory lung responses (10,12,33).…”

“…Osteopontin is a key cytokine recently shown to associate with granulomatous inflammation, regardless of cause (17)(18)(19)(20). Osteopontin induces leukocyte chemotaxis, and is produced by alveolar macrophages.…”

Immunolocalization of IFN-gamma in the lesions of resistant and susceptible mice to Paracoccidioides brasiliensis infection

“…On the other hand, at later phase of infection, resistant mice showed a higher IFN-c staining in lymphomononuclear cells compared with susceptible mice, suggesting the presence of protective immune mechanisms to the control of fungal dissemination through the high activation status of phagocytes, as previously described . Therefore, susceptible mice although able to produce IFN-c since the early stage of the infection, could not control the fungal dissemination, as demonstrated by the several loose granulomas containing viable fungal cells, indicating their incapacity to control the infection, and confirmed by the higher fungal load in omentum lesions of B10.A than in A/J mice previously observed by the same authors (Nishikaku et al, 2008).…”

“…In our experimental model of P. brasiliensis infection, we could detect distinct patterns of ECM components using immunohistochemical reactions (Xidieh et al, 1999;Nishikaku & Burger, 2003a, b), the presence of some cytokines (Nishikaku & Burger, 2003a;Nishikaku et al, 2008) and of proteolytic enzymes (Nishikaku et al, 2009a) at the lesions of infected mouse strains.…”

“…The immunohistochemical reactions were done according to the protocol described previously (Nishikaku & Burger, 2003a;Nishikaku et al, 2008). In brief, slides with deparaffinized tissue sections were incubated overnight at 4°C with anti-mouse IFN-c mAb (hybridoma XMG 1.2, dilution in PBS -0.3% Tween 20).…”