Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis - 26/03/24

Doi : 10.1016/j.tube.2024.102495

Lihui Guo ^a,^⁎,^{^{1
These authors contributed equally to this work.}} , Stefan-Dan Zaharie ^b,^{^{1
These authors contributed equally to this work.}}, A. Marceline van Furth ^c,^{^{2
These authors contributed equally to this work.}}, Nicole N. van der Wel ^d, Anita E. Grootemaat ^d, Lin Zhang ^e, Marianna Bugiani ^f, Mariana Kruger ^g, Martijn van der Kuip ^c,^{^{2
These authors contributed equally to this work.}}, René Lutter ^a,^h,^{^{2
These authors contributed equally to this work.}}
^a Department of Experimental Immunology, Amsterdam UMC, Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands
^b Department of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa and National Health Laboratory Services, Francie Van Zijl Dr, Parow, Tygerberg Hospital, Cape Town, 7505, South Africa
^c Department of Pediatric Infectious Diseases and Immunology, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands
^d Electron Microscopy Center Amsterdam, Department of Medical Biology, Amsterdam UMC, Location Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
^e Neuropsychiatric Disorders Lab, Neuroimmunology Group, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
^f Department of Pathology, Amsterdam UMC, Location VU University Medical Center, De Boelelaan 1117, 1081, HV Amsterdam, the Netherlands
^g Department of Pediatrics, Faculty of Health Sciences, Stellenbosch University and Tygerberg Hospital, Francie van Zijl Dr, Parow, Bellville, Cape Town, 7505, South Africa
^h Pulmonary Medicine, Amsterdam UMC, Location Academic Medical Center, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands

^⁎Corresponding author.

Abstract

In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%.

Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of M. tuberculosis as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with M. tuberculosis. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.

Le texte complet de cet article est disponible en PDF.

Keywords : Indoleamine 2,3-dioxygenase 1, Indoleamine 2,3-dioxygenase 2, Tuberculous meningitis, Granuloma, 3-Hydroxy anthranilic acid, Quinolinic acid, Apoptosis, Autophagy

Plan

Introduction

Materials and methods

IDO1 and IDO2 expression in TBM brain

Kynurenine metabolites in TBM brain

AHR, apoptosis and autophagy in TBM brain

Presence of M. tuberculosis in brain tissue

Extracellular DNA traps in TBM brain

Discussion

Funding

CRediT authorship contribution statement

Export

Vol 146

Article 102495- mai 2024 Retour au numéro

Article précédent

Analysis of T-lymphocyte subsets and risk factors in children with tuberculosis
Wei-Wei Ma, Ling-Chao Wang, De-An Zhao, Na Wei, Jun-Wei Cui, Shu-Jun Li

| Article suivant

Lysosomal enzymes and the oxygen burst capability of monocyte-derived macrophages in active drug-resistant tuberculosis patients in relation to cell attachment
Febriana Catur Iswanti, Kurnia Maidarmi Handayani, Ardiana Kusumaningrum, Tomohiko Yamazaki, Diah Handayani, Mohamad Sadikin

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis - 26/03/24

Abstract

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL