Paracoccidioidomycosis: characterization of subpopulations of macrophages and cytokines in human mucosal lesions

Abstract

Mucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes β-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.

β2 Integrin-Mediated Susceptibility to Paracoccidioides brasiliensis Experimental Infection in Mice

“…As described for other systemic mycoses, cellular immune response, mediated mainly by IFN-g activated macrophages, is the host's major defense mechanism against PCM (Bocca et al, 1999;Souto et al, 2000;Souto et al, 2003;Schimke et al, 2017). Activated macrophages show a fundamental role during all the disease outcomes, along with granuloma formation, to protect the host against the dissemination of the infection (Bocca et al, 1999;Souto et al, 2000;Pagliari et al, 2019). Granuloma formation relies on the secretion of cytokines such as IFN-g and TNF-a, which confer resistance against Pb by macrophage activation, fungal contention, and nitric oxide (NO) production, resulting in the killing of the pathogen (Pagliari et al, 2019).…”

“…Activated macrophages show a fundamental role during all the disease outcomes, along with granuloma formation, to protect the host against the dissemination of the infection (Bocca et al, 1999;Souto et al, 2000;Pagliari et al, 2019). Granuloma formation relies on the secretion of cytokines such as IFN-g and TNF-a, which confer resistance against Pb by macrophage activation, fungal contention, and nitric oxide (NO) production, resulting in the killing of the pathogen (Pagliari et al, 2019). Furthermore, IFN-g modulates chemokines and chemokine receptors' macrophage expression and the lung cellular infiltration pattern in mice experimentally infected with Pb (Souto et al, 2000).…”

“…Although the host cellular immune response shows an essential role against infection, the interaction mechanisms involved in macrophage activation have not yet been thoroughly described. Due to the complexity of the interaction between the host and Pb, various studies have attempted to unveil the fungus' innate host defense mechanisms (Calich et al, 2008;Pagliari et al, 2019). The interaction of host macrophages and Pb is mediated by cell surface receptors on the outer membrane of the macrophage, including mannose receptor, Ctype lectin receptors (CTLR), such as dectin-1, Toll-like receptor 2 (TLR-2), TLR-4, surfactant protein, scavenger receptor, and complement receptor types 3 (CR3) and 4 (CR4) (Jimenez Mdel et al, 2006;Calich et al, 2008;Tan, 2012;Feriotti et al, 2013).…”