Talaromycosis-associated immune reconstitution inflammatory syndrome exhibits immune dysregulation in patients with acquired immunodeficiency syndrome
- 1Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, China
- 2Guangzhou Medical Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, China
- 3Infectious Diseases Department, Foshan First People’s Hospital, Foshan, China
Abstract
Background: Talaromycosis (TSM) is a severe opportunistic fungal infection that mostly infects patients with acquired immunodeficiency syndrome (AIDS). After antiretroviral therapy (ART), AIDS patients with TSM may develop immune reconstitution inflammatory syndrome (IRIS), leading to the paradoxical worsening of clinical symptoms. However, the immunological characteristics of TSM-related IRIS (TSM-IRIS) in AIDS patients remain poorly understood. Methodology/Principal Findings: We conducted a longitudinal cohort study of AIDS patients with TSM and analyzed the immunological features using flow cytometry, transcriptome, and multiplex cytokine assays at admission, ART initiation, and at 2, 4 weeks after ART initiation. Patients with TSM-IRIS displayed significantly higher baseline CD3 ⁺ T cells at admission and lower frequencies of PD-1 ⁺ CD4 ⁺ T cells at ART initiation than those without IRIS (non-IRIS). After ART initiation, TSM-IRIS was associated with dynamic transcriptomic changes involving inflammatory and immune-related pathway enrichment, along with sustained elevations of interleukin (IL)-17, IL-21, C-X-C motif chemokine ligand (CXCL) 5, and CXCL12. Transcriptomic analysis revealed the dynamic enrichment of pro-inflammatory pathways prior to and during the early phase of ART. Conclusion/Significance: AIDS patients with TSM-IRIS exhibited an immune profile associated with enhanced T cell activation, characterized by accelerated immune reconstitution accompanied by heightened inflammatory activity during the early phase of ART, may potentially acting as the immune markers for prediction or diagnosis of TSM-IRIS in AIDS patients. Author summary: For patients with acquired immunodeficiency syndrome (AIDS), initiating antiretroviral therapy (ART) typically restores immune function and improves clinical outcomes. However, following ART initiation, restored immunity to specific infectious or non-infectious antigens may result in paradoxical clinical worsening or new disease. In this study, we monitored and compared immunological features in AIDS patients with talaromycosis (TSM) who developed immune reconstitution inflammatory syndrome (IRIS) with those without IRIS during ART treatment. We found that patients with TSM-IRIS exhibited an earlier rise in CD3+ T cells at admission and lower frequencies of PD-1+ CD4+ T cells at ART initiation than patients without IRIS. Overall, our study described the accelerated immune reconstitution accompanied by heightened inflammatory activity in TSM-IRIS, a phenomenon with limited prior evidence.
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BibTeX
@article{zhao2026talaromycosisassociated,
title = {{Talaromycosis-associated immune reconstitution inflammatory syndrome exhibits immune dysregulation in patients with acquired immunodeficiency syndrome}},
author = {Bei Zhao and Qinzhi Zhang and Pengle Guo and Yingyin Yang and Feilong Xu and Xuemei Ling and Kaiyin He and Xiejie Chen and Xiaoping Tang and Huihua Zhang and Linghua Li},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = sep,
doi = {10.1371/journal.pntd.0014695},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014695},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Talaromycosis-associated immune reconstitution inflammatory syndrome exhibits immune dysregulation in patients with acquired immunodeficiency syndrome
AU - Bei Zhao
AU - Qinzhi Zhang
AU - Pengle Guo
AU - Yingyin Yang
AU - Feilong Xu
AU - Xuemei Ling
AU - Kaiyin He
AU - Xiejie Chen
AU - Xiaoping Tang
AU - Huihua Zhang
AU - Linghua Li
PY - 2026
DA - 2026/09/01
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014695
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014695
AB - Background: Talaromycosis (TSM) is a severe opportunistic fungal infection that mostly infects patients with acquired immunodeficiency syndrome (AIDS). After antiretroviral therapy (ART), AIDS patients with TSM may develop immune reconstitution inflammatory syndrome (IRIS), leading to the paradoxical worsening of clinical symptoms. However, the immunological characteristics of TSM-related IRIS (TSM-IRIS) in AIDS patients remain poorly understood. Methodology/Principal Findings: We conducted a longitudinal cohort study of AIDS patients with TSM and analyzed the immunological features using flow cytometry, transcriptome, and multiplex cytokine assays at admission, ART initiation, and at 2, 4 weeks after ART initiation. Patients with TSM-IRIS displayed significantly higher baseline CD3 ⁺ T cells at admission and lower frequencies of PD-1 ⁺ CD4 ⁺ T cells at ART initiation than those without IRIS (non-IRIS). After ART initiation, TSM-IRIS was associated with dynamic transcriptomic changes involving inflammatory and immune-related pathway enrichment, along with sustained elevations of interleukin (IL)-17, IL-21, C-X-C motif chemokine ligand (CXCL) 5, and CXCL12. Transcriptomic analysis revealed the dynamic enrichment of pro-inflammatory pathways prior to and during the early phase of ART. Conclusion/Significance: AIDS patients with TSM-IRIS exhibited an immune profile associated with enhanced T cell activation, characterized by accelerated immune reconstitution accompanied by heightened inflammatory activity during the early phase of ART, may potentially acting as the immune markers for prediction or diagnosis of TSM-IRIS in AIDS patients. Author summary: For patients with acquired immunodeficiency syndrome (AIDS), initiating antiretroviral therapy (ART) typically restores immune function and improves clinical outcomes. However, following ART initiation, restored immunity to specific infectious or non-infectious antigens may result in paradoxical clinical worsening or new disease. In this study, we monitored and compared immunological features in AIDS patients with talaromycosis (TSM) who developed immune reconstitution inflammatory syndrome (IRIS) with those without IRIS during ART treatment. We found that patients with TSM-IRIS exhibited an earlier rise in CD3+ T cells at admission and lower frequencies of PD-1+ CD4+ T cells at ART initiation than patients without IRIS. Overall, our study described the accelerated immune reconstitution accompanied by heightened inflammatory activity in TSM-IRIS, a phenomenon with limited prior evidence.
SN - 1935-2735
ER -