Failure of nitric oxide production by macrophages and decrease in CD4+ T cells in oral paracoccidioidomycosis: possible mechanisms that permit local fungal multiplication

Abstract

Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific inflammatory and immune response. The participation of nitric oxide (NO), a product of the inducible nitric oxide synthase enzyme (iNOS), as an important fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated. In order to further characterize the Oral Paracoccidioidomycosis (OP), we undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+, CD68+ cells and mast cells. The samples were distributed in groups according to the number of viable fungi per mm2. Our results showed weak immunolabeling for iNOS in the multinucleated giant cells (MNGC) and in most of the mononuclear (MN) cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to Control (clinically healthy oral tissues). Additionally, our analysis revealed a similarity in the number of CD4+ cells between the Control and the OP groups with higher numbers of fungi. These findings suggest that a low expression of iNOS and a decrease in the CD4+ T cells in OP may represent possible mechanisms that permit the local fungal multiplication and maintenance of active oral lesions.

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

“…The following species were investigated: C. neoformans , Sporothrix schenckii (Romero-Martinez et al 2000), P. brasiliensis (Gomez et al 2001, da Silva et al 2006, Fonsecaea pedrosoi (Alviano et al 2004), Aspergillus fumigatus (Youngchim et al 2004) and C. posadasii (Nosanchuk et al 2007). Generally, a cellular immune response appears to be the most effective defence mechanism against both experimental and human PCM (Calich et al 1994, Marques Mello et al 2002, Batista et al 2005. Macrophages have a pivotal role in innate immunity, due to their ability to phagocytose and kill microorganisms, as well as to attract and activate other cell types, which are critical to the immune response (Linehan et al 2000).…”

The relation between FoxP3+ regulatory T cells and fungal density in oral paracoccidioidomycosis: a preliminary study

“…Contradictory results were obtained by Batista et al . where CD4 + cells were decreased in oral PCM and a higher number of viable yeast cells were observed, suggesting that a reduction in CD4 + cells may allow fungal proliferation and maintenance of active oral lesions.…”

“…Immunohistochemical studies were performed as described previously . Treg cells were identified using antibodies against FoxP3 (clone 236AE7; Santa Cruz Biotechnology, Santa Cruz, CA, USA; at 1 : 100) overnight at 4 °C.…”

Nitric oxide participation in granulomatous response induced by Paracoccidioides brasiliensis infection in mice

“…Clinical Wndings from PCM patients showed low iNOS expression by macrophages and giant cells in active oral granulomatous lesions [1], as well as a small number of iNOS-positive macrophages and giant cells in granulomas of oral mucosa and lymph nodes of patients with, respectively, localized adult and juvenile forms of PCM [30]. These authors suggested that iNOS expression is down regulated in the granulomatous lesions, representing a possible mechanism of fungal evasion from the host's immune response.…”