Immunological Responses to Sporothrix Fungal Infections

Sporothrix species trigger a coordinated innate and adaptive immune response following cutaneous or subcutaneous entry. Initial recognition by phagocytes is mediated through pattern‐recognition receptors such as dectin-1 and Toll-like receptors, leading to production of pro-inflammatory cytokines including TNFα, IL-1β and IL-6. β-Glucan exposure on the fungal cell wall and glycoprotein adhesins such as Gp70 influence receptor engagement, phagocytosis and release of neutrophil extracellular traps. A robust Th1/Th17 adaptive response characterised by IFN-γ and IL-17 promotes macrophage activation and fungal clearance, whereas IL-10 dampens tissue damage. Humoral immunity, long regarded as secondary, is now recognised for antibody-mediated opsonisation of yeasts and enhancement of phagocytic killing. Transcriptomic analyses of patient lesions have revealed upregulation of JAK/STAT signalling components, suggesting potential targets for immunomodulation. Together, these mechanisms determine the severity, localisation and resolution of sporotrichosis and guide the development of immunotherapeutic strategies and vaccines.

Research from Nature Portfolio

Whole-transcriptome sequencing of skin lesion samples from patients infected with Sporothrix globosa has uncovered hundreds of differentially expressed long non-coding RNAs, microRNAs and messenger RNAs. Enrichment analyses pinpointed activation of innate immune pathways and upregulation of SOCS3, IL-6 and JAK3, implicating the JAK/STAT axis as a novel therapeutic target. Concurrent protein analyses confirmed increased phosphorylation of JAK3 and STAT3 in infected tissues, providing molecular insight into host–fungus signalling dynamics. An immunoproteomic study in a murine subcutaneous model identified three peptides from S. brasiliensis antigens that bind MHC-class II and elicit strong cellular immunity. One peptide derived from Gp70 induced elevated CD4+ T-cell responses and high levels of IFN-γ, IL-17A and IL-1β, correlating with increased neutrophil recruitment and fungal clearance. These findings support peptide-based vaccine development against sporotrichosis.

Immunological Responses to Sporothrix Fungal Infections publication trend

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

Technical terms

Beta-1,3-glucan: A polysaccharide in the fungal cell wall recognised by dectin-1 to activate innate immunity.

Dectin-1: A C-type lectin receptor on phagocytes that binds β-glucan and triggers cytokine release.

Gp70: A 70-kDa cell-wall glycoprotein adhesin central to Sporothrix virulence and a target for antibody-based therapies.

JAK/STAT pathway: A signalling cascade activated by cytokines that regulates gene expression in immune cells.

Th17 cells: A subset of CD4+ T cells producing IL-17 that contribute to antifungal defence and neutrophil recruitment.

References

1. Whole transcriptome sequencing for revealing the pathogenesis of sporotrichosis caused by Sporothrix globosa. Scientific Reports (2024).
2. Silencing of Sporothrix schenckii GP70 Reveals Its Contribution to Fungal Adhesion, Virulence, and the Host–Fungus Interaction. Journal of Fungi (2024).
3. An immunoproteomic approach revealing peptides from Sporothrix brasiliensis that induce a cellular immune response in subcutaneous sporotrichosis. Scientific Reports (2018).
4. Immunity and Treatment of Sporotrichosis. Journal of Fungi (2018).