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Antifungal immunity: advances in PRR recognition, adaptive responses, and immune-based therapies
Jianlin Zhou1,2, Xueni Lu1,2, Ruirui He1,2
1The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, China.
Abstract:
As a common disease in human life, fungal infection poses a serious threat to human life and health. Moreover, owing to the rapid development of the immune escape mechanisms of fungi and the emergence of new drug-resistant fungi, existing therapeutic drugs are no longer able to meet the treatment needs of patients. In particular, the World Health Organization (WHO) published the first Fungal Priority Pathogens List (FPPL) in 2022, further emphasizing that we need to pay more attention to invasive fungal infections. In addition, the WHO has called for increased global investment in fungal infections and the development of antifungal drugs. In this review, we introduce the mechanism by which innate immune cell PRRs recognize fungal pathogen PAMPs, the role of adaptive immune cells in antifungal immunity, fungal infections caused by immune deficiencies, and the latest research progress in immune-based fungal therapies.
Insights
Fungal infections are a growing threat due to drug resistance and immune evasion. This review explores innate and adaptive immune responses and advances in immune-based antifungal therapies.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Fungal infections pose a significant global health challenge, exacerbated by emerging drug-resistant strains and fungal immune evasion.
- The World Health Organization (WHO) identified the urgent need for new antifungal strategies with its 2022 Fungal Priority Pathogens List (FPPL).
- Current antifungal treatments are becoming less effective, necessitating novel therapeutic approaches.
Purpose of the Study:
- To review the mechanisms of fungal recognition by the innate immune system through pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs).
- To elucidate the critical role of adaptive immune cells in combating fungal infections.
- To discuss the implications of immune deficiencies in susceptibility to fungal diseases and highlight recent advancements in immune-based antifungal therapies.
Main Methods:
- This review synthesizes current research on innate and adaptive immune responses to fungal pathogens.
- It examines the molecular mechanisms of fungal recognition and immune cell activation.
- The review also covers the impact of host immune status on fungal infection outcomes and evaluates novel immunotherapeutic strategies.
Main Results:
- Innate immune cells utilize PRRs to detect fungal PAMPs, initiating crucial early defense responses.
- Adaptive immunity, involving T cells and antibodies, plays a vital role in controlling and clearing fungal infections.
- Immune deficiencies significantly increase the risk and severity of invasive fungal diseases.
- Emerging immune-based therapies show promise in overcoming limitations of conventional antifungals.
Conclusions:
- Understanding fungal-host immune interactions is key to developing effective antifungal strategies.
- Targeting innate and adaptive immune pathways offers a promising avenue for novel antifungal treatments.
- Continued research and investment in immune-based therapies are essential to address the growing threat of invasive fungal infections.
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