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

• Published in: Communications biology Vol. 7; no. 1; p. 524
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 14; 45; 45/91; 631/250/255; 631/250/255/1715; Adult; Anergy; Biomedical and Life Sciences; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell-mediated immunity; Chronic Disease; Chronic illnesses; Coinfection - immunology; Ethiopia; Female; HIV; HIV Infections - complications; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immunotherapy; Leishmaniasis, Visceral - complications; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Life Sciences; Lymphocytes; Lymphocytes T; Male; Middle Aged; Parasitic diseases; PD-1 protein; Transcriptomes; Visceral leishmaniasis; γ-Interferon; Ethiopia
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06225-2

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. A longitudinal study of the circulatory cellular immunity of individuals co-infected with recurrent visceral leishmaniasis and HIV suggests that T cell unresponsiveness underlies visceral leishmaniasis chronicity.