Penicillium Marneffei Infections in Immunocompromised Patients

Penicillium marneffei is a thermally dimorphic fungus endemic to Southeast Asia that poses a life-threatening risk in patients with impaired cell-mediated immunity. Historically linked to advanced HIV disease, the spectrum of susceptible hosts has expanded to include individuals receiving immunosuppressive therapies, transplant recipients and those with primary immunodeficiencies. Inhalation of conidia leads to yeast-phase replication in macrophages and dissemination via the bloodstream, resulting in febrile illness, hepatosplenomegaly, pulmonary infiltrates, cutaneous lesions and occasionally osteolysis. Diagnosis relies on fungal culture, histopathology and emerging molecular assays, yet delays remain common, contributing to high morbidity and mortality. Standard treatment comprises amphotericin B induction followed by itraconazole maintenance, although toxicity, drug interactions and relapse challenge long-term management. Recent work has uncovered pathogen strategies for evading host defences and highlighted the interplay between fungal genetics, immune status and clinical outcome. Growing recognition of talaromycosis as a neglected tropical mycosis has spurred calls for universal screening in at-risk populations, optimisation of rapid diagnostics and development of targeted immunotherapies to improve prognosis and curb global disease burden.

Research from Nature Portfolio

High-throughput transcriptomic analysis of human macrophages infected with P. marneffei demonstrates that the fungus induces alternative splicing of the NCOR2/SMRT gene, producing a truncated co-repressor isoform that limits histone acetylation and suppresses pro-inflammatory cytokine release. This mechanism, orchestrated by the splicing regulator TUT1, reveals a novel pathway of immune evasion and suggests that modulating host splicing factors could restore effective macrophage fungicidal activity and inform new therapeutic strategies.

Penicillium Marneffei Infections in Immunocompromised Patients publication trend

The graph below shows the total number of articles in penicillium marneffei infections in immunocompromised patients across all publications each year (not limited to Nature Index journals).

Technical terms

Thermally dimorphic fungus: An organism that grows as a mould at environmental temperatures and converts to a yeast form at body temperature.

Alternative splicing: A regulatory process where a single gene can give rise to multiple mRNA variants through differential exon inclusion.

Co-repressor: A protein that binds transcription factors to repress gene expression, often by altering chromatin structure.

Disseminated mycosis: A fungal infection that spreads from the original site into multiple organs via the bloodstream.

CD4+ T-cell: A type of lymphocyte essential for orchestrating adaptive immune responses and activating macrophages.

References

1. Talaromyces marneffei suppresses macrophage inflammation by regulating host alternative splicing. Communications Biology (2023).
2. Impact of pathogen genetics on clinical phenotypes in a population of Talaromyces marneffei from Vietnam. Genetics (2023).
3. The microbial damage and host response framework: lesson learned from pathogenic survival trajectories and immunoinflammatory responses of Talaromyces marneffei infection. Frontiers in Immunology (2024).
4. Burden of Talaromyces marneffei infection in people living with HIV/AIDS in Asia during ART era: a systematic review and meta-analysis. BMC Infectious Diseases (2020).
5. A global call for talaromycosis to be recognised as a neglected tropical disease. The Lancet Global Health (2021).