The Role of the Interleukin-17 Axis and Neutrophils in the Pathogenesis of Endemic and Systemic Mycoses.

Juan David Puerta-Arias,Ángel González,Susana P Mejía

doi:10.3389/fcimb.2020.595301

Abstract

Systemic and endemic mycoses are considered life-threatening respiratory diseases which are caused by a group of dimorphic fungal pathogens belonging to the genera Histoplasma, Coccidioides, Blastomyces, Paracoccidioides, Talaromyces, and the newly described pathogen Emergomyces. T-cell mediated immunity, mainly T helper (Th)1 and Th17 responses, are essential for protection against these dimorphic fungi; thus, IL-17 production is associated with neutrophil and macrophage recruitment at the site of infection accompanied by chemokines and proinflammatory cytokines production, a mechanism that is mediated by some pattern recognition receptors (PRRs), including Dectin-1, Dectine-2, TLRs, Mannose receptor (MR), Galectin-3 and NLPR3, and the adaptor molecules caspase adaptor recruitment domain family member 9 (Card9), and myeloid differentiation factor 88 (MyD88). However, these PRRs play distinctly different roles for each pathogen. Furthermore, neutrophils have been confirmed as a source of IL-17, and different neutrophil subsets and neutrophil extracellular traps (NETs) have also been described as participating in the inflammatory process in these fungal infections. However, both the Th17/IL-17 axis and neutrophils appear to play different roles, being beneficial mediating fungal controls or detrimental promoting disease pathologies depending on the fungal agent. This review will focus on highlighting the role of the IL-17 axis and neutrophils in the main endemic and systemic mycoses: histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis.

Highlights

Systemic fungal infections are characterized by their ability to produce a potentially life-threatening respiratory disease
2018; Cao et al, 2019; Schwartz et al, 2019; Schwartz and Kauffman, 2020). These mycoses are usually geographically restricted; histoplasmosis is found worldwide, coccidioidomycosis is endemic in some regions of the United States and some countries of Latin America, blastomycosis is endemic in North America and Africa, paracoccidioidomycosis is restricted to Latin America, talaromycosis is endemic in Asian countries, while emergomycosis has been reported in Africa, Europe, Asia, and North America (Sepúlveda et al, 2017; Turissini et al, 2017; Kirkland and Fierer, 2018; Cao et al, 2019; Schwartz et al, 2019; Schwartz and Kauffman, 2020)
Th17 and IL-17 protective responses, which participate during the primary infections in the nonimmune host, are associated with recruiting and activating neutrophils and macrophages to the site of infection as well as with chemokine and proinflammatory cytokines production, a mechanism mediated by the fungal recognition of pattern recognition receptors (PRRs) present on the surface of the host cells, which lead to the activation of adaptor molecules and the subsequent downstream signaling (Wüthrich et al, 2011; Nanjappa et al, 2012; Wu et al, 2013; Ketelut-Carneiro et al, 2019)

Summary

Introduction

Systemic fungal infections are characterized by their ability to produce a potentially life-threatening respiratory disease. When the mice were immunized with a liveattenuated vaccine against coccidioidomycosis, the vaccineinduced protection promoted early recruitment and elevated numbers of neutrophils to the infection site, suggesting that the role of these phagocytic cells depends on prior exposure of the host to Coccidioides spp.

Results

Conclusion