Paracoccidioides brasiliensis conidia recognize fibronectin and fibrinogen which subsequently participate in adherence to human type II alveolar cells: Involvement of a specific adhesin

A 32-Kilodalton Hydrolase Plays an Important Role in Paracoccidioides brasiliensis Adherence to Host Cells and Influences Pathogenicity

“…More recently, Gonzalez and coworkers identified a 32-kDa protein in cell wall protein extracts of both forms of P. brasiliensis that was capable of binding to various ECM proteins, including laminin, fibronectin, and fibrinogen (14). Additionally, they demonstrated that this 32-kDa protein is involved in the initial conidial adherence to pulmonary epithelial cells that express ECM proteins on the surface, acting as a bridge between the two cell types (13).…”

Pulmonary Paracoccidioidomycosis: Clinical, Immunological and Histopathological Aspects

“…The fibrosis process begins with acute injury caused by the interaction of P. brasiliensis conidia with ECM proteins and lung epithelial cells; this interaction is followed by chronic granulomatous inflammation with fibroblast proliferation and activation, an increase in ECM proteins predominantly composed of fibronectin, fibrinogen, collagen type I and III, as observed in the surroundings of the granulomas. These EM proteins contribute to the establishment of fibronodular lesions that continue to advance even after appropriate antifungal therapy with itraconazole, a medication that effectively controls the active stage of this mycosis but does not hinder lung fibrosis (González et al, 2008a, c;Naranjo et al, 2010;Tobón et al, 2003). Even though patients with chronic PCM show well-established pulmonary lesions at diagnosis, all of them are not in the same stage of infection development, explaining why, although not sequentially, several studies have been able to describe certain histological patterns present during the development of fibrosis in humans.…”

“…In reference to PCM animal models, several have been developed with the purpose of understanding the complete course of the disease; despite differences on the inoculum used (infective forms and concentration), fungal isolates, route of inoculation and host genetic background, the results have made it possible to define certain common phases during the granulomatous inflammation process (Burger et al, 1996;Calich et al, 1985;Da Silva et al, 2009;Xidieh et al, 1999). However, only the murine model of chronic pulmonary PCM in male BALB/c mice induced by the intranasal inoculation of naturally infective conidia has provided a reproducible model to observe in detail not only the characteristics of the inflammatory response induced by P. brasiliensis conidia, but also the important components of the PCM residual form (Cock et al, 2000;González et al, 2008a;Restrepo et al, 1992). In the murine model described above, it was determined that at 4 weeks post-infection, when the granuloma are well shaped, thin fibers of collagen and reticulin became evident, suggesting the beginning of a fibrotic process, which progressed simultaneously with the presence of leukocyte infiltrates surrounding the granuloma .…”

Lung Diseases - Selected State of the Art Reviews

“…In addition, it has been reported that the different fungal morphotypes of P. brasiliensis (conidia, yeast cells and mycelia) exhibit on their surface adhesin-type molecules that allow both binding to several ECM proteins -mainly fibronectin, fibrinogen and laminin -and adherence to epithelial cells (Caro et al, 2008;González et al, 2005aGonzález et al, , 2008aHernández et al, 2010). Activation of pulmonary cells, mainly Ms, took place after fungal interaction, thus initiating the inflammatory process through production of pro-inflammatory cytokines and chemokines, which in turn induced the expression of adhesion molecules on the leukocytes' surface (González et al, 2003(González et al, , 2005b).…”

“…The fibrosis process begins with acute injury caused by the interaction of P. brasiliensis conidia with ECM proteins and lung epithelial cells; this interaction is followed by chronic granulomatous inflammation with fibroblast proliferation and activation, an increase in ECM proteins predominantly composed of fibronectin, fibrinogen, collagen type I and III, as observed in the surroundings of the granulomas. These EM proteins contribute to the establishment of fibronodular lesions that continue to advance even after appropriate antifungal therapy with itraconazole, a medication that effectively controls the active stage of this mycosis but does not hinder lung fibrosis (González et al, 2008a, c;Naranjo et al, 2010;Tobón et al, 2003). Even though patients with chronic PCM show well-established pulmonary lesions at diagnosis, all of them are not in the same stage of infection development, explaining why, although not sequentially, several studies have been able to describe certain histological patterns present during the development of fibrosis in humans.…”