Role of TLR-2 and Fungal Surface Antigens on Innate Immune Response AgainstSporothrix schenckii

Abstract

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2(-/-) animals. The results showed that TLR-2(-/-) animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2(-/-). The absence of TLR-2 led to lower production of the cytokines TNF-α, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii.

Sporothrix schenckii sensu stricto and Sporothrix brasiliensis Are Differentially Recognized by Human Peripheral Blood Mononuclear Cells

“…The receptors TLR2 and TLR4 have been demonstrated to be relevant during the control of S. schenckii sensu stricto in a murine model of sporotrichosis (Sassá et al, 2012; Negrini et al, 2013). Here, we confirm these data using primary immune cells and demonstrated that they are also relevant during the interaction of S. brasiliensis with immune cells.…”

“…Using the animal model of sporotrichosis, it has been demonstrated that TLR4 recognizes lipidic extracts from yeast cells and triggers the production of both pro- and anti-inflammatory cytokines (Sassá et al, 2009, 2012). Furthermore, TLR2 also contributes to the recognition of this organism, participating in the phagocytosis of yeast cells by macrophages, and the production of both pro- and anti-inflammatory cytokines (Negrini et al, 2013). Using human THP-1-derived macrophages, MR has been involved in the phagocytosis of S. schenckii conidia (Guzman-Beltran et al, 2012).…”

Immunoproteomic analysis reveals a convergent humoral response signature in the Sporothrix schenckii complex

“…564humoral response against a diversity of Sporothrix antigens 565 expressed during infection[49][50][51][52]. Such protein heteroge-566 neity may trigger the humoral response [19,53] and generate 567 specific protective antibodies against the evolution of 568 Sporothrix infection [27,29,54].…”

Letter from the Editor

“…In addition, several manuscripts focusing on IL-1 (Ban et al, 2012, Cruz-Robles et al, 2009Latella et al, 2009;Rafferty et al, 2010),TH 2 cells (Durrant & Metzger, 2010;Zoghi et al, 2011), and Toll-like receptors (Cohen et al, 2012, Cordeau et al, 2012, Jha et al, 2011Negrini et al, 2013), which are some of the players of this immune interaction have been published recently in Immunological Investigations, and these authors may be well served to be alerted to the interaction that these molecules and cells have with bone growth and resorption.…”

“…In addition, popular articles in 2013 include: CD8þ T cell exhaustion during persistent viral infection is regulated independently of the virus-specific T cell receptor (Jackson et al, 2013); Measurement of suppressor activity of T CD4þCD25þ T reg cells using bromodeoxyuridine incorporation assay (Avalos-Martin, 2013); IL-17 gene polymorphism is associated with chronic periodontitis and periimplantitis in Iranian Patients: A cross-sectional study (Kadkhodazadeh et al, 2013); Biomarkers of lung injury in critical care medicine: Past, present, and future (Tunceroglu et al, 2013); Reconstitution and phenotype of tregs in CMV reactivating patients following allogeneic hematopoietic stem cell transplantation (Velaga et al, 2013); Immunological studies of reactive oxygen species damaged catalase in patients with Systemic Lupus Erythematosus: Correlation with Disease Activity Index (Al-Shobaili et al, 2013); Role of TLR-2 and fungal surface antigens on innate immune response against Sporothrix schenckii (Negrini et al, 2013); Intracellular CTLA4 and regulatory T cells in patients with laryngeal squamous cell carcinoma (Erfani et al, 2013); Protection Against Cyclophosphamide-Induced Myelosuppression by ZPDC Glycoprotein (24 kDa) (Lee & Lim, 2013).…”