Dectin-1 Facilitates IL-18 Production for the Generation of Protective Antibodies Against Candida albicans.

Hui Shen,Wei-Tong Hou,Yi-Da Wang,Yuan-Li Chen,Xi-Ran Qiu,Shi-Yu Guo,Liangjing Lu,Yuan-Ying Jiang,Yuetian Yu,Si-Min Chen,Juan-Juan Sun,Wei Fang,Yu Zhang,Mao-Mao An,Xin-Yu Hu,Zui Zou

doi:10.3389/fmicb.2020.01648

Abstract

Invasive candidiasis (IC) is one of the leading causes of death among immunocompromised patients. Because of limited effective therapy treatment options, prevention of IC through vaccine is an appealing strategy. However, how to induce the generation of direct candidacidal antibodies in host remains unclear. Gpi7 mutant C. albicans is an avirulent strain that exposes cell wall β-(1,3)-glucans. Here, we found that vaccination with the gpi7 mutant strain could protect mice against invasive candidiasis caused by C. albicans and non-albicans Candida spp. The protective effects induced by gpi7 mutant relied on long-lived plasma cells (LLPCs) secreting protective antibodies against C. albicans. Clinically, we verified a similar profile of IgG antibodies in the serum samples from patients recovering from IC to those from gpi7 mutant-vaccinated mice. Mechanistically, we found cell wall β-(1,3)-glucan of gpi7 mutant facilitated Dectin-1 receptor dependent nuclear translocation of non-canonical NF-κB subunit RelB in macrophages and subsequent IL-18 secretion, which primed protective antibodies generation in vivo. Together, our study demonstrate that Dectin-1 engagement could trigger RelB activation to prime IL-18 expression and established a new paradigm for consideration of the link between Dectin-1 mediated innate immune response and adaptive humoral immunity, suggesting a previously unknown active vaccination strategy against Candida spp. infection.

Highlights

Invasive candidiasis (IC) is one of leading death causes among hospitalized individuals, especially immunocompromised patients (Kullberg and Arendrup, 2015; McCarty and Pappas, 2016)
The results demonstrated that neutralizing anti-IFN-γ antibody (Figure 3B) or anti-IL-17 antibody (Figure 3C) did not affect the immunoprotection against C. albicans infection induced by gpi7 mutant vaccination
The results indicated that gpi7 mutant-vaccination could protect against C. albicans or nonalbicans Candida spp. caused systematic infection, suggesting that the proteins targeted by the antibodies produced after gpi7 mutant-vaccination may share similarity among Candida spp

Summary

INTRODUCTION

Invasive candidiasis (IC) is one of leading death causes among hospitalized individuals, especially immunocompromised patients (Kullberg and Arendrup, 2015; McCarty and Pappas, 2016). Recent studies have highlighted the crucial roles of TH1 and TH17 cell-mediated immunity in host defense against infection caused Candida spp., both protective immune serum and antibodies have shown remarkable efficacy (Bugli et al, 2013; Drummond et al, 2014; Verma et al, 2014) These findings have special relevance for vaccination, especially in partly or totally immunocompromised individuals. This study found that the gpi mutant C. albicans with surface β-(1,3)-glucan exposure could induce hosts to generate protective antibodies against IC in mice and demonstrated that IL-18 plays a central role in the type 2 response contributing to this immunoprotection. We verified a similar profile of IgG antibodies in serum samples from patients recovering from IC to those of gpi mutant-vaccinated mice

MATERIALS AND METHODS

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT

Findings

ETHICS STATEMENT