The Predominance of Alternatively Activated Macrophages Following Challenge with Cell Wall Peptide-Polysaccharide After Prior Infection with Sporothrix schenckii

Abstract

Sporotrichosis is a subcutaneous mycosis that is caused by the dimorphic fungus Sporothrix schenckii. This disease generally occurs within the skin and subcutaneous tissues, causing lesions that can spread through adjacent lymphatic vessels and sometimes leading to systemic diseases in immunocompromised patients. Macrophages are crucial for proper immune responses against a variety of pathogens. Furthermore, macrophages can play different roles in response to different microorganisms and forms of activation, and they can be divided into "classic" or "alternatively" activated populations, as also known as M1 and M2 macrophages. M1 cells can lead to tissue injury and contribute to pathogenesis, whereas M2 cells promote angiogenesis, tissue remodeling, and repair. The aim of this study was to investigate the roles of M1 and M2 macrophages in a sporotrichosis model. Toward this end, we performed phenotyping of peritoneal exudate cells and evaluated the concomitant production of several immunomediators, including IL-12, IL-10, TGF-β, nitric oxide, and arginase-I activity, which were stimulated ex vivo with cell wall peptide-polysaccharide. Our results showed the predominance of the M2 macrophage population, indicated by peaks of arginase-I activity as well as IL-10 and TGF-β production during the 6th and 8th weeks after infection. These results were consistent with cellular phenotyping that revealed increases in CD206-positive cells over this period. This is the first report of the participation of M2 macrophages in sporotrichosis infections.

Comparative efficacy and toxicity of two vaccine candidates against Sporothrix schenckii using either Montanide™ Pet Gel A or aluminum hydroxide adjuvants in mice

“…Maia et al [43] showed a predominantly Th1 ex vivo cytokine release profile in the initial stages of infection and a Th2 predominance in later stages. Aligned with this, our group has previously shown the occurrence of M1 and M2 macrophages in the initial and late phase of the S. schenckii infection, respectively, matching this cytokine pattern [44]. M1 and M2 macrophages are stimulated by Th1 and Th2 cytokines, respectively [45].…”

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

“…The highest production of IL-1β, TNF-α, IL-10 and NO was observed in the group infected with 0.10%. A balanced production of the proinflammatory IL-1β, TNF-α and the antinflammatory cytokine IL-10 is estimulated during S. schenckii infection (Alegranci et al ., 2013; Maia et al ., 2016). However, although NO is also stimulated and it has an antifungal effect in vitro against this fungus, it also seems to have an immunosuppressive effect that favors fungal infection (Fernandes et al ., 2008; Gonzalves et al ., 2015).…”

Dectin-1 expression by macrophages and related antifungal mechanisms in a murine model of Sporothrix schenckii sensu stricto systemic infection

“…Early activation of the immune system largely depends on pattern recognition receptors (PRRs), many of which involved in the recognition of fungal pathogens [6,7]. Several studies performed in our lab evidenced a role for different PRRs, including the Toll-like receptors (TLRs) 2 [8] and 4 [9,10] and the NOD-like receptor (NLR) family member NLRP3 [11], as important innate components triggered during the S. schenckii infection.…”