Immunological Responses to Invasive Fungal Infections

Invasive fungal infections pose a significant threat to immunocompromised individuals worldwide, exploiting vulnerabilities in both innate and adaptive immunity. The first line of defence comprises pattern recognition receptors on macrophages and dendritic cells, which detect fungal cell-wall components such as β-glucans and mannans. Engagement of receptors like Dectin-1 and Toll-like receptors triggers phagocytosis, activation of Bruton's tyrosine kinase (BTK) pathways and assembly of inflammasomes, leading to cytokine release and recruitment of neutrophils and inflammatory monocytes. Neutrophils then generate an oxidative burst and release antimicrobial peptides and extracellular traps to contain and kill hyphae. Concurrently, monocytes differentiate into dendritic cells that prime T helper subsets, notably Th1 and Th17 cells, which secrete interferon-γ and interleukin-17 to enhance macrophage fungicidal activity and orchestrate granulocyte responses. Adaptive B-cell responses produce opsonising antibodies that facilitate phagocyte clearance. Dysregulation of any of these steps—due to genetic defects, immunosuppressive therapy or fungal evasion strategies—can lead to unchecked fungal proliferation and tissue invasion. Understanding these interconnected mechanisms has guided development of adjunctive immunotherapies and informed risk stratification in transplant recipients and patients with haematological malignancies.

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Immunological Responses to Invasive Fungal Infections publication trend

The graph below shows the total number of articles in immunological responses to invasive fungal infections across all publications each year (not limited to Nature Index journals).

Technical terms

Pattern recognition receptor (PRR): A germline-encoded molecule that recognises conserved fungal cell-wall motifs to initiate immune signalling.

Dectin-1: A C-type lectin receptor on phagocytes that binds β-glucans and activates downstream antifungal responses.

Bruton's tyrosine kinase (BTK): A signalling enzyme in neutrophils and B cells essential for phagocyte activation and antibody production.

Inflammasome: A cytosolic multiprotein complex that activates inflammatory caspases and promotes interleukin-1β maturation.

Oxidative burst: Rapid generation of reactive oxygen species by NADPH oxidase in phagocytes to kill ingested fungi.

Phagocytosis: The process by which immune cells engulf and internalise pathogens for destruction.

Cytokine: A small secreted protein that mediates communication between immune cells to regulate inflammation and host defence.

References

1. BTK drives neutrophil activation for sterilizing antifungal immunity. Journal of Clinical Investigation (2024).
2. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infectious Diseases (2014).
3. Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus. PLOS Pathogens (2017).