Understanding the genetic basis of immune responses to fungal infection

ABSTRACT

Introduction

Fungal infections represent a global public health problem that affects millions of people. Despite remarkable advances achieved over the last decades, available diagnostic and therapeutic tools remain insufficient for the optimal management of these diseases. The clinical course of fungal infection is highly variable, and evidence accumulated from patients with rare mutations and cohort-based studies suggests that the trajectory of disease is largely defined by patient genetics and its impact on immune responses. Therefore, there is an urgent need to elucidate the precise mechanisms by which genetic variants influence the risk, progression, and outcome of fungal infection.

Areas covered

In this review, we highlight recent advances in our understanding of the genetic factors that influence antifungal immune responses based on candidate gene studies and genome-wide approaches performed in different experimental and clinical models.

Expert opinion

Research on genetics of susceptibility to infection is expected to lead to a detailed knowledge framework for the pathogenesis of human fungal infections and unveil novel targets and pathways amenable to clinical intervention.

KEYWORDS:

• Fungal infection
• antifungal immunity
• genetic susceptibility
• functional genomics
• personalized medicine

Declaration of Interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors had substantially contributed to the conception and design of the review article, interpretation of the relevant literature, drafting the review article and/or revising it for intellectual content.

Article highlights

• This review describes common genetic variations associated with the risk of fungal infection.

• Mechanisms of genetic association that involve altered immune responses to fungal infection are highlighted.

• This review suggests the usefulness of host genetics for the design of personalized diagnostic and therapeutic approaches for fungal infection.

Additional information

Funding

Funding support was provided by the Fundação para a Ciência e a Tecnologia (FCT) (PTDC/SAU-SER/29635/2017, UIDB/50026/2020, and UIDP/50026/2020), the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000039), the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 847507, the ‘la Caixa’ Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003, and the Gilead Research Scholars Program - Antifungals. Individual support was provided by FCT (SFRH/BD/136814/2018 to SMG and CEECIND/04058/2018 to CC).