Abstract
Neutrophils are essential to control several fungal infections. These cells are commonly known for their pro-inflammatory activities. However, some studies have demonstrated the anti-inflammatory properties of neutrophils during certain infectious diseases, culminating in the inhibition of T cell proliferation. Chromoblastomycosis (CBM) is a deep and progressive mycosis that affects thousands of people worldwide. Although neutrophil infiltrates are observed in the lesion histopathology, the fungus can overtake the immune system response and destroy the host-infected tissue. The present study demonstrated that neutropenic animals had an increase in the IL-6 production in the spleen and liver, followed by a lower fungal burden in these organs up to 14 days of infection. Neutropenic animals also showed a lower F. pedrosoi-specific antibody production 14-days post infection and higher T-cell proliferation in the in vitro experiments after stimulation with F. pedrosoi-purified proteins. Taken together, our results suggest that the presence of regulatory neutrophils in the mouse model of F. pedrosoi infection could act favoring the spread of the fungus and the chronicity of the infection. These findings shed light on the CBM treatment, which might target neutrophil polarization as a new therapy approach to treat CBM lesions.
Highlights
Neutrophils are essential to control several fungal infections
Our group demonstrated that neutrophils eliminate F. pedrosoi conidia in vitro through Toll-like receptors (TLRs)-2 and TLR-4-dependent phagocytosis and ROS production, whereas hyphal killing occurs through Neutrophil Extracellular Traps (NETs) released independently of ROS production and TLR-2/TLR-4 r eceptors[17]
Since neutrophils with suppressor features were recently observed in Cryptococcus neoformans[26], Aspergillus fumigatus[27], and Candida albicans[28,29] infections, we wondered whether F. pedrosoi could modulate the neutrophils activities in vivo, leading to the inhibition of the host immune response and the chronicity of the infection
Summary
Neutrophils are essential to control several fungal infections These cells are commonly known for their pro-inflammatory activities. In 2007, the term PMN myeloid-derived suppressor cells (PMN-MDSCs) was suggested to designate these anti-inflammatory neutrophils[25] This cell is usually studied in a cancer context, it is known to be related to other pathological conditions, such as autoimmune and infectious diseases. Since CBM infection is a chronic fungal disease with chronic skin lesions characterized by severe neutrophils and macrophages infiltrated, we hypothesized whether these neutrophils were modulated by the fungus to a PMN-MDSC profile, favoring the fungal survival and the chronicity of the infection. Our results suggest that F. pedrosoi modulates neutrophils to an anti-inflammatory/PMN-MDSC profile with implications for host protection in the CBM infection
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