Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection.

Aiysha Thompson,Aiysha Thompson,Diogo M Da Fonseca,Louise Walker,Diogo M Da Fonseca,Philip R Taylor,Selinda J Orr,Selinda J Orr,Neil A R Gow,Neil A R Gow,Neil A R Gow,James S Griffiths,James S Griffiths,Philip R Taylor

doi:10.3389/fmicb.2021.633229

Abstract

More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.

Highlights

Candida spp. are the second most common agents of human fungal infection after dermatophytes (Brown et al, 2012)
The significant differences in the Candida cell walls in length/type of mannan structures present may affect the immune response mediated by C-type lectin-like receptors (CLRs), such as Dectin-2 and Mincle in response to these different clinically relevant Candida spp
We found that Mincle and Dectin-2 are involved in regulating cytokine production in response to all four Candida spp

Summary

Introduction

Candida spp. are the second most common agents of human fungal infection after dermatophytes (Brown et al, 2012). C. albicans is the most virulent and frequently isolated pathogen from patients with invasive candidiasis, accounting for 50–70% of all infections (Pfaller and Diekema, 2007; Guinea, 2014), invasive infections caused by other non-albicans Candida spp., such as C. parapsilosis, C. glabrata, and C. tropicalis and recently C. auris have been rising over the past decades (Arendrup et al, 2002; Yapar, 2014; Lamoth et al, 2018), and pose an emerging health concern. Most research tends to focus on C. albicans as a model pathogen of candidiasis, with much less research on other clinically relevant Candida spp

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Conclusion