Abstract

Neutrophils are the first leukocytes recruited to the site of infection and are thought to be responsible for fungal elimination from the skin such as dermatophytes. Neutrophils are able to secrete reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) that can kill different fungi, including Aspergillus, spp., Candida albicans, and Phialophora verrucosa. However, NET production in response to Trichophyton rubrum, the main etiologic agent of dermatophytosis, has yet to be studied. We demonstrated that human neutrophils produce NETs against different morphotypes of T. rubrum in a dose-dependent manner and NET formation is dependent on ROS production. In addition, ROS production by human neutrophils in response to T. rubrum is dependent on NADPH oxidase, but not on fungal viability. NETs mediated killing of T. rubrum. Collectively, these results demonstrate that T. rubrum was able to trigger the production of NETs, suggesting that these extracellular structures may represent an important innate immune effector mechanism controlling physiological response to T. rubrum infection.

Highlights

  • This study aimed to elucidate the ability of different morphotypes of T. rubrum to induce reactive oxygen species (ROS) production and neutrophil extracellular traps (NETs) release by human neutrophils

  • We could observe structures compatible with NETs in neutrophils incubated with both morphotypes of T. rubrum (Figure 1A)

  • We previously showed that chronic widespread dermatophytosis patients’ neutrophils presented reduced hydrogen peroxide (H2 O2 ) production when compared with healthy donors [16]

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Summary

Introduction

Dermatophytoses are superficial fungal infections of keratinized structures, and the main etiological agent in humans is Trichophyton rubrum. It is considered an anthropophilic dermatophyte, well adapted to humans, usually causing mild inflammation and cutaneous lesions [1]. Neutrophils are the most abundant leukocytes in the blood, being the first cells to arrive at an infection site [5] Their main antifungal function is due to their phagocytosis ability and their potent antimicrobial arsenal composed of antimicrobial peptides, neutrophil-specific proteolytic enzymes, as well as their production of reactive oxygen species (ROS) [6,7]

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