Transcriptional profile of Mycobacterium tuberculosis infection in people living with HIV

Burcu Tepekule; Lisa Jörimann; Corinne D Schenkel; Lennart Opitz; Jasmin Tschumi; Rebekka Wolfensberger; Kathrin Neumann; Katharina Kusejko; Marius Zeeb; Lucas Boeck; Marisa Kälin; Julia Notter; Hansjakob Furrer; Matthias Hoffmann; Hans H Hirsch; Alexandra Calmy; Matthias Cavassini; Niklaus D Labhardt; Enos Bernasconi; Gabriela Oesch; Karin J Metzner; Dominique L Braun; Huldrych F Günthard; Roger D Kouyos; Fergal Duffy; Johannes Nemeth; Swiss HIV Cohort Study

doi:10.1016/j.isci.2024.111228

Transcriptional profile of Mycobacterium tuberculosis infection in people living with HIV

iScience. 2024 Oct 21;27(11):111228. doi: 10.1016/j.isci.2024.111228. eCollection 2024 Nov 15.

Authors

Burcu Tepekule^{1

2

3}, Lisa Jörimann^{1

2}, Corinne D Schenkel^{1

2}, Lennart Opitz⁴, Jasmin Tschumi^{1

2}, Rebekka Wolfensberger¹, Kathrin Neumann^{1

2}, Katharina Kusejko¹, Marius Zeeb^{1

2}, Lucas Boeck⁵, Marisa Kälin¹, Julia Notter⁶, Hansjakob Furrer⁷, Matthias Hoffmann⁸, Hans H Hirsch^{9

10

11}, Alexandra Calmy¹², Matthias Cavassini¹³, Niklaus D Labhardt^{14

15}, Enos Bernasconi^{12

16

17}, Gabriela Oesch¹⁸, Karin J Metzner^{1

2}, Dominique L Braun^{1

2}, Huldrych F Günthard^{1

2}, Roger D Kouyos^{1

2}, Fergal Duffy¹⁹, Johannes Nemeth¹; Swiss HIV Cohort Study

Affiliations

¹ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
² Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
³ Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA.
⁴ Functional Genomics Center Zurich, Swiss Federal Institute of Technology and University of Zurich, Zurich, Switzerland.
⁵ Department of Biomedicine, University of Basel, Basel, Switzerland.
⁶ Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St. Gallen, Switzerland.
⁷ Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁸ Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital Olten, Olten, Switzerland.
⁹ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
¹⁰ Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
¹¹ Department Biomedicine, Transplantation and Clinical Virology, University of Basel, Basel, Switzerland.
¹² Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
¹³ Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
¹⁴ Division Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
¹⁵ University of Basel, Basel, Switzerland.
¹⁶ Division of Infectious Diseases, Ente Ospedaliero Cantonale, Lugano, Switzerland.
¹⁷ University of Geneva and University of Southern Switzerland, Lugano, Switzerland.
¹⁸ Department of Child Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁹ Seattle Children's Research Institute, Seattle, WA, USA.

Abstract

In people with HIV-1 (PWH), Mycobacterium tuberculosis (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals. Functional annotation identified alterations in IL-6, TNF, and KRAS pathways. Notably, MTB-related genes displayed an inverse correlation with HIV-1 viremia, at both individual and signature score levels. These findings suggest that MTB infection in PWH induces a shift in immune system activation, inversely related to HIV-1 viral load. These results may explain the observed enhanced antiretroviral control in MTB-infected PWH. This study highlights the complex interplay between MTB and HIV-1, emphasizing the importance of understanding their interaction for managing co-infections in this population.

Keywords: Health sciences; Microbiology; Transcriptomics.