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Review
. 2021 Feb 10:12:633047.
doi: 10.3389/fmicb.2021.633047. eCollection 2021.

Role for IL-1 Family Cytokines in Fungal Infections

James S Griffiths  1 , Giorgio Camilli  1 , Natalia K Kotowicz  1 , Jemima Ho  1 , Jonathan P Richardson  1 , Julian R Naglik  1
Affiliations
Review

Role for IL-1 Family Cytokines in Fungal Infections

James S Griffiths et al. Front Microbiol. .

Abstract

Fungal pathogens kill approximately 1.5 million individuals per year and represent a severe disease burden worldwide. It is estimated over 150 million people have serious fungal disease such as recurrent mucosal infections or life-threatening systemic infections. Disease can ensue from commensal fungi or new infection and involves different fungal morphologies and the expression of virulence factors. Therefore, anti-fungal immunity is complex and requires coordination between multiple facets of the immune system. IL-1 family cytokines are associated with acute and chronic inflammation and are essential for the innate response to infection. Recent research indicates IL-1 cytokines play a key role mediating immunity against different fungal infections. During mucosal disease, IL-1R and IL-36R are required for neutrophil recruitment and protective Th17 responses, but function through different mechanisms. During systemic disease, IL-18 drives protective Th1 responses, while IL-33 promotes Th2 and suppresses Th1 immunity. The IL-1 family represents an attractive anti-fungal immunotherapy target. There is a need for novel anti-fungal therapeutics, as current therapies are ineffective, toxic and encounter resistance, and no anti-fungal vaccine exists. Furthering our understanding of the IL-1 family cytokines and their complex role during fungal infection may aid the development of novel therapies. As such, this review will discuss the role for IL-1 family cytokines in fungal infections.

Keywords: Aspergillus; Candida; IL-1; fungal immunology; fungi.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
A schematic representation of IL-1 family receptors, co-receptors, and ligands. Each ligand, receptor and co-receptor are separated into their appropriate IL-1 subfamily. An arrow indicates the induction of signaling; a flat line indicates the blocking of signaling. The latest nomenclature is used, for previous/alternative nomenclature see Table 1.
FIGURE 2
FIGURE 2
A schematic representation of the role of IL-1 family cytokines in fungal immunity. Each ligand is separated into their appropriate IL-1 subfamily. The icons for Candida, Aspergillus, Cryptococcus, and Paracoccidioides are labeled at the top of the figure. The presence of a fungal icon underneath a cytokine indicates induction. Arrows and blocked lines represent the functional outcome of this cytokine following induction.
See this image and copyright information in PMC

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