Immune intervention avenues to control fungal infections in immunocompromised individuals

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Background

Invasive fungal infections have been on the rise in recent years. It is estimated that more than 1 billion people are infected with some forms of fungi, accounting for ~1.6 million deaths/year, surpassing tuberculosis. Despite the global rise in fungal infections, no licensed vaccine is available. In particular, infections with a variety of fungi such as Candida, Aspergillus, Cryptococcus, Pneumocystis, Coccidioides, Histoplasma, Blastomyces, Paracoccidiodes, Mucormycetes, Taloromycetes, and other rare opportunistic yeasts and molds cause higher morbidity and mortality in ever-expanding immunocompromised patients, which is compounded by challenges in early diagnosis and the frequent occurrence of antifungal resistance. Individuals with weakened immune systems due to genetic and acquired CD4+ T cell lymphopenia, dysbiosis, cancer therapies, transplantations, immunotherapies, use of immunosuppressive drugs, and following viral infections such as influenza or SARS COV2 are most vulnerable.

With limited available arsenals of antifungal drugs that are frequently associated with toxicity and are prone to the emergence of drug-resistant fungal strains, immune enhancement interventions represent a major unmet need in these frail and severely immunocompromised hosts. The mechanisms of antifungal immunity are multifaceted and involve both the innate and adaptive components of the immune system. The current understanding of fungal control involves the robust activation of innate cells, including macrophages, dendritic cells, and neutrophils, for fungicidal activity with the support of proinflammatory cytokines expressed by fungal-specific adaptive immune cells. Therapeutically, engineered fungal-specific T cells or NK cells have the potential to directly contain the fungi by inhibiting growth/survival. Furthermore, immune regulators of innate and adaptive immunity have been identified, including new adjuvants to bolster antifungal immunity. The use or targeting of such elements will lead to the discovery of newer immunotherapeutics.

Our greater understanding of immunity against fungal infections has paved many potential therapeutic interventions targeting both innate and adaptive immune effector cells to restore functional immunity or enhance fungal-specific immune responses. We welcome the submissions of Original Research, Review, Mini-Review, and Perspective articles focusing on, but not limited to, the following sub-topics:
• Restoration of functional adaptive immunity
• Pathogenic fungal-host interactions
• Novel modulators of innate immunity
• Innate immune cells for therapeutics
• Targeting negative regulators of innate and adaptive immunity
• Exploiting or bolstering residual adaptive immunity (CD8+ T cells and B cells) under CD4+ T cell deficiency
• Use of therapeutic engineered T cells and NK cells
• Mechanisms of immune dysfunction for susceptibility to fungal infections

Keywords: Fungal infections, interventions, immunocompromised, antifungal immune therapies

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