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Persistent T cell unresponsiveness associated with chronic visceral leishmaniasis in HIV-coinfected patients.

作者信息

de Vrij Nicky, Pollmann Julia, Rezende Antonio M, Ibarra-Meneses Ana V, Pham Thao-Thy, Hailemichael Wasihun, Kassa Mekibib, Bogale Tadfe, Melkamu Roma, Yeshanew Arega, Mohammed Rezika, Diro Ermias, Maes Ilse, Domagalska Malgorzata A, Landuyt Hanne, Vogt Florian, van Henten Saskia, Laukens Kris, Cuypers Bart, Meysman Pieter, Beyene Hailemariam, Sisay Kasaye, Kibret Aderajew, Mersha Dagnew, Ritmeijer Koert, van Griensven Johan, Adriaensen Wim

机构信息

Clinical Immunology Unit, Department of Clinical Sciences, Institute of Tropical Medicine, 2000, Antwerp, Belgium.

Adrem Data Lab, Department of Computer Science, University of Antwerp, 2020, Antwerp, Belgium.

出版信息

Commun Biol. 2024 May 3;7(1):524. doi: 10.1038/s42003-024-06225-2.

DOI:10.1038/s42003-024-06225-2
PMID:38702419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11068874/
Abstract

A large proportion of HIV-coinfected visceral leishmaniasis (VL-HIV) patients exhibit chronic disease with frequent VL recurrence. However, knowledge on immunological determinants underlying the disease course is scarce. We longitudinally profiled the circulatory cellular immunity of an Ethiopian HIV cohort that included VL developers. We show that chronic VL-HIV patients exhibit high and persistent levels of TIGIT and PD-1 on CD8/CD8 T cells, in addition to a lower frequency of IFN-γ TIGIT CD8/CD8 T cells, suggestive of impaired T cell functionality. At single T cell transcriptome and clonal resolution, the patients show CD4 T cell anergy, characterised by a lack of T cell activation and lymphoproliferative response. These findings suggest that PD-1 and TIGIT play a pivotal role in VL-HIV chronicity, and may be further explored for patient risk stratification. Our findings provide a strong rationale for adjunctive immunotherapy for the treatment of chronic VL-HIV patients to break the recurrent disease cycle.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/29faa6e53a72/42003_2024_6225_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/dd0b24b1947f/42003_2024_6225_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/b2bdc35c3ea6/42003_2024_6225_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/27a3d09dfd3c/42003_2024_6225_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/779284e94580/42003_2024_6225_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/2ce4ad4f22e7/42003_2024_6225_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/c7cb7a74c95d/42003_2024_6225_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/29faa6e53a72/42003_2024_6225_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/dd0b24b1947f/42003_2024_6225_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/b2bdc35c3ea6/42003_2024_6225_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/27a3d09dfd3c/42003_2024_6225_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/779284e94580/42003_2024_6225_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/2ce4ad4f22e7/42003_2024_6225_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/c7cb7a74c95d/42003_2024_6225_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e3/11068874/29faa6e53a72/42003_2024_6225_Fig7_HTML.jpg

相似文献

[1]
Persistent T cell unresponsiveness associated with chronic visceral leishmaniasis in HIV-coinfected patients.

Commun Biol. 2024-5-3

[2]
Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV.

Cell Rep Med. 2022-1-18

[3]
T-cell activation and senescence in asymptomatic HIV/Leishmania infantum co-infection.

PLoS Negl Trop Dis. 2025-3-17

[4]
Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8 T Cells Are Associated With the Cure of Human Visceral sis.

Front Immunol. 2021

[5]
High levels of CD4⁺ CTLA-4⁺ Treg cells and CCR5 density in HIV-1-infected patients with visceral leishmaniasis.

Eur J Clin Microbiol Infect Dis. 2015-2

[6]
Impaired Thymic Output Can Be Related to the Low Immune Reconstitution and T Cell Repertoire Disturbances in Relapsing Visceral Leishmaniasis Associated HIV/AIDS Patients.

Front Immunol. 2020

[7]
Pre- & post-treatment evaluation of immunological features in Indian visceral leishmaniasis (VL) patients with HIV co-infection.

Indian J Med Res. 2006-3

[8]
Visceral leishmaniasis as an independent cause of high immune activation, T-cell senescence, and lack of immune recovery in virologically suppressed HIV-1-coinfected patients.

HIV Med. 2015-4

[9]
The Risk and Predictors of Visceral Leishmaniasis Relapse in Human Immunodeficiency Virus-Coinfected Patients in Ethiopia: A Retrospective Cohort Study.

Clin Infect Dis. 2017-10-30

[10]
Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

Front Cell Infect Microbiol. 2018-3-29

引用本文的文献

[1]
AI-driven analysis by identifying risk factors of VL relapse in HIV co-infected patients.

Sci Rep. 2025-7-1

[2]
Visceral leishmaniasis in heavily pretreated multiple myeloma patients a case series of 17 patients from the Mediterranean Coast of Spain.

Ann Med. 2025-12

[3]
Serum sPD-1 as a marker of T cell exhaustion in ART-naïve, ART-experienced, and intestinal parasite co-infected HIV-positive adults at the university of Gondar comprehensive specialized hospital, Northwest Ethiopia, 2024.

BMC Infect Dis. 2025-5-27

[4]
Insights to the HIV-associated visceral leishmaniasis clinical outcome: lessons learned about immune mediated disorders.

Front Immunol. 2025-3-12

[5]
The development and maintenance of immunity against visceral leishmaniasis.

Front Immunol. 2024-12-9

[6]
Prediction of visceral leishmaniasis development in a highly exposed HIV cohort in Ethiopia based on Leishmania infection markers: results from the PreLeisH study.

EBioMedicine. 2024-12

本文引用的文献

[1]
Immune checkpoint inhibitor combinations-current and emerging strategies.

Br J Cancer. 2023-4

[2]
Recurrent visceral leishmaniasis relapses in HIV co-infected patients are characterized by less efficient immune responses and higher parasite load.

iScience. 2022-12-23

[3]
T Lymphocyte Exhaustion During Human and Experimental Visceral Leishmaniasis.

Front Immunol. 2022

[4]
Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8 T cell responses.

Immunity. 2022-3-8

[5]
scGate: marker-based purification of cell types from heterogeneous single-cell RNA-seq datasets.

Bioinformatics. 2022-4-28

[6]
Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV.

Cell Rep Med. 2022-1-18

[7]
Navigating the pitfalls of applying machine learning in genomics.

Nat Rev Genet. 2022-3

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clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.

Innovation (Camb). 2021-7-1

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Nat Rev Mol Cell Biol. 2022-1

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Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies.

Nat Rev Drug Discov. 2022-7

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