Immunological Responses to Paracoccidioides Brasiliensis Infections

Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis, triggers a complex interplay between innate and adaptive immunity. Early recognition by pattern recognition receptors on macrophages and dendritic cells—most notably Dectin-1, Toll-like receptors and the NLRP3 inflammasome—drives pro-inflammatory cytokine release including IL-1β, TNF-α, IFN-γ and IL-17. Neutrophils and monocyte subsets migrate to the lung, forming granulomas that contain yeast cells but also establish niches for fungal persistence. Adaptive responses hinge on a protective Th1/Th17 axis, while Th2-skewed or excessive regulatory T-cell (Treg) activity correlates with susceptibility and chronic disease. Myeloid-derived suppressor cells (MDSCs) and indoleamine 2,3-dioxygenase (IDO-1) further modulate local T-cell function, balancing clearance of the fungus against tissue damage. Host genetic variation in receptors such as Dectin-1 influences cytokine profiles and disease outcome, underscoring the importance of personalised approaches in endemic regions.

Research from Nature Portfolio

Recent studies have demonstrated that MDSCs infiltrate infected lungs and exert immunosuppressive actions via IDO-1, dampening Th1 and Th17 responses and exacerbating fungal burden. Inhibition of IDO-1 in these cells restores protective T-cell proliferation and leads to reduced pathology in murine models. Moreover, signalling through Dectin-1, TLR2 and TLR4 has been shown to govern IDO-1 induction in MDSCs, revealing an integrated network of pattern recognition receptor–mediated immunoregulation that shapes disease severity and identifies the MDSC–IDO-1 axis as a promising adjuvant therapeutic target.

Immunological Responses to Paracoccidioides Brasiliensis Infections publication trend

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

Technical terms

Paracoccidioides brasiliensis: Thermally dimorphic fungus responsible for systemic paracoccidioidomycosis.

Myeloid-derived suppressor cells (MDSCs): Heterogeneous myeloid population that potently suppresses T-cell responses.

Indoleamine 2,3-dioxygenase (IDO-1): Enzyme catalysing tryptophan degradation with immunoregulatory effects.

Pattern recognition receptors (PRRs): Innate receptors such as Dectin-1 and TLRs that detect conserved microbial molecules.

Dectin-1: C-type lectin receptor recognising fungal β-glucans and initiating innate responses.

Toll-like receptors (TLRs): Family of receptors recognising diverse pathogen-associated molecular patterns.

T helper subsets (Th1, Th17, Treg): CD4+ T-cell lineages mediating pro-inflammatory (Th1, Th17) or regulatory (Treg) functions.

Extracellular vesicles (EVs): Membrane-enclosed nanoparticles secreted by cells carrying proteins and nucleic acids.

Granuloma: Structured aggregate of immune cells formed to contain persistent pathogens.

References

1. Myeloid-derived suppressor cells are associated with impaired Th1 and Th17 responses and severe pulmonary paracoccidioidomycosis which is reversed by anti-Gr1 therapy. Frontiers in Immunology (2023).
2. Extracellular vesicles from virulent P. brasiliensis induce TLR4 and dectin-1 expression in innate cells and promote enhanced Th1/Th17 response. Virulence (2024).
3. The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling. Scientific Reports (2023).
4. Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis-Induction of Cytokine Production in Peripheral Blood Mononuclear Cells. Journal of Fungi (2023).
5. NOD-Like Receptor P3 Inflammasome Controls Protective Th1/Th17 Immunity against Pulmonary Paracoccidioidomycosis. Frontiers in Immunology (2017).