Recognition of laminin byParacoccidioides brasiliensisconidia: a possible mechanism of adherence to human type II alveolar cells

Abstract

This study addresses the recognition of laminin by Paracoccidioides brasiliensis conidia, as well as its possible role in the adherence of conidia to A549 cells. Adherence of conidia to immobilized laminin was shown to be specific, as anti-laminin antibodies, soluble laminin or the laminin-derived peptides IKVAV and CDPGYIGSR inhibited this interaction. RGD containing peptides and various monosaccharides had no effect on adherence, with the exception of N-acetylneuraminic acid. Pre-treatment of conidia with fibrinogen and fibronectin, but not with BSA, also resulted in significant inhibition, suggesting that P. brasiliensis conidia might cross-recognize host proteins involved in colonization. In assays using transmission electron microscopy, we observed internalization of conidia 30 min after exposition to A549 cells. Laminin present on the surface of A549 cells shown to serve as mediator of this interaction, with a significant decrease in fungal adherence when the epithelial cells were pre-treated with anti-laminin antibodies or when conidia were pre-incubated with either soluble laminin or the laminin-specific peptides. Together these results suggest that the recognition of laminin by P. brasiliensis conidia is a key process in the interaction with pulmonary epithelial cells, where this extracellular matrix protein acts as bridging molecule.

Interaction between Paracoccidioides brasiliensis conidia and the coagulation system: involvement of fibrinogen

“…Furthermore, P. brasiliensis expresses adhesin molecules on its own surface, allowing adhesion to ECM proteins and host cells (Gonzalez et al. 2005, 2008a, Caro et al 2008, Donofrio et al 2009, Nogueira et al 2010). One of these molecules is a 32-kDa molecule that belongs to an HAD superfamily that confers to P. brasiliensis the capacity to bind to fibrinogen and other ECM proteins (Gonzalez et al 2005, 2008a).…”

“…As in other fungal infections (e.g., histoplasmosis, cryptococcosis, coccidioidomycosis and blastomycosis) (Klein & Tebbets 2007), the mechanisms used by this fungal pathogen to cause infection and dissemination in the host are unclear, but during the initial interaction of P. brasiliensis conidia with host tissue components, both extracellular matrix (ECM) proteins and epithelial/endothelial cells are most likely involved (Patti & Hook 1994, Caro et al 2008, Gonzalez et al 2008a). These interactions could also participate in the dissemination process.…”

“…In our pulmonary PCM murine model, infected animals show increased ECM protein expression (mainly fibrinogen, fibronectin and laminin) in the lungs during the acute phase of infection (Gonzalez et al 2008b). In addition, fibrinogen inhibits the adherence and internalisation of P. brasiliensis conidia in alveolar type II cells (Caro et al 2008, Gonzalez et al 2008a). This finding suggests a role for fibrinogen in fungal adherence to host tissues.…”

Lung Diseases - Selected State of the Art Reviews

“…In additional studies, we observed an increase of in situ lysozyme expression (PMN and Ms) in the lungs of mice infected with P. brasiliensis conidia during the first 4 days post-challenge. This expression was accompanied by a decrease in the number of fungal propagules (González et al, 2008), observations suggesting that lysozymes may exert an antifungal effect against P. brasiliensis. Altogether, the above observations led us to propose a description of the initial mechanism triggered by the infection with P. brasiliensis conidia: 1.…”

“…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).…”