Importance of complement 3 and mannose receptors in phagocytosis ofParacoccidioides brasiliensisconidia byNramp1congenic macrophages lines

Abstract

Genetic factors influence susceptibility to Paracoccidioidomycosis, a Latin American endemic mycosis. The pattern of susceptibility of congenic mouse strains infected with Paracoccidioides brasiliensis resembles the pattern of the Nramp1 gene. Thus, congenic murine bone-marrow-derived macrophage lines B10R (Nramp1rGly169) and B10S (null Nramp1 protein expression, Nramp1sAsp169) were infected with P. brasiliensis conidia and compared, under opsonic and nonopsonic conditions. Opsonization increased the percentage of phagocytosis by both cell lines. B10R macrophages exhibited a higher percentage of cells with associated conidia and higher number of conidia per macrophage than B10S. Heat-inactivation and EDTA treatment of serum used for opsonization, and treatment of macrophages with anti-complement receptor 3 (CR3) decreased phagocytosis by both cell lines. alpha-methyl-d-mannoside reduced phagocytosis by B10R macrophages, suggesting that the mannose receptor participates in phagocytosis by these cells. The CR3 expression was similar on both cell lines and B10R expressed more mannose receptors, but neither cell line expressed CR1. IFNgamma decreased the conversion of conidia to the yeast form of P. brasiliensis in B10R, but not in B10S macrophages.

Resistance of melanized yeast cells of Paracoccidioides brasiliensis to antimicrobial oxidants and inhibition of phagocytosis using carbohydrates and monoclonal antibody to CD18

“…The involvement of CR3 and mannose receptor in the uptake of opsonized and nonopsonized P. brasiliensis conidia was documented (Jimenez et al 2006). We have shown previously that mannan can partially inhibit phagocytosis of P. brasiliensis yeasts (da Silva et al 2006).…”

Transcriptional response of murine macrophages upon infection with opsonized Paracoccidioides brasiliensis yeast cells

“…Clec1b is able to recognise mannose residues present on the surface of a wide spectrum of microorganisms, including P. brasiliensis [28]. Recently, additional evidence of its importance for the phagocytosis of P. brasiliensis has been obtained by the treatment of macrophages with an analogous methyl-mannoside that reduced the frequency of internalized fungus [29]; in this context, our results are in accordance with this report showing that the up-regulation of Clec1b is probably important for a more effective fungal internalization. Additionally, an induction of other cellular adhesion molecules (ICAM-1, VCAM-1, CD18 and Mac-1) in lungs of mice infected with P. brasiliensis have been observed participating in the inflammatory process and therefore in the pathogenesis of paracoccidiodomycosis [7,8].…”

TLR2 Is a Negative Regulator of Th17 Cells and Tissue Pathology in a Pulmonary Model of Fungal Infection

“…It is known, however, that normal macrophages are permissive to P. brasiliensis growth while cytokineactivated macrophages are able to restrain P. brasiliensis multiplication (22). It was previously demonstrated that C3b, mannose receptor, and gp43, the immunodominant Ag of P. brasiliensis, play an important role in the initial interaction between P. brasiliensis cells and mouse peritoneal macrophages (23)(24)(25). Interestingly, a recent work of our laboratory demonstrated that alveolar macrophages from susceptible mice are easily activated by IL-12 and IFN-␥ and display an efficient fungal killing associated with increased secretion of NO and proinflammatory cytokines.…”