Disease progression is associated with differential neutrophil maturation in <i>Mycobacterium tuberculosis</i> –infected macaques
Abstract
Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is associated with clinical diversity and outcomes ranging from latent TB to active TB with distinct pathophysiologies. However, our understanding of the innate immune mechanisms related to the protection or progression of TB is limited. Among innate immune cells, the role of neutrophils is not fully elucidated, as they have been shown to exhibit both protective and harmful capacities in TB. We hypothesized that Mtb infection induces changes in neutrophil phenotype and function, influencing the infection outcomes. Based on clinical, bacteriological, and positron emission tomography with x-ray computed tomography (PET/CT) scan parameters, cynomolgus macaques infected by Mtb were stratified into two categories: animals that rapidly progressed to an active form of TB, designated as “fast progressors,” and “slow progressors,” which include low symptomatic or asymptomatic animals. In this study, we identified transcriptomic signatures of type I interferons and neutrophil degranulation in macaques with fast progression to active TB, which were not observed in animals with slow TB progression. Unsupervised mass cytometry analysis showed the emergence of blood immature neutrophils (CD101+ CD10−) in fast-progressing animals. In addition, bulk blood neutrophils from infected animals displayed capacities to modulate TNF-α production and cytotoxic function of CD8 T cells in a contact-dependent mechanism. In lung granulomas, neutrophils showed a tissue-specific phenotype (CD101− CD10+), with greater infiltration in animals with active TB. These data suggest that neutrophil subpopulations are associated with disease progression, with capacities to modulate CD8 T cells’ functions, which in turn may contribute to disease progression.
Article Details
Journal Info
The Journal of Immunology
American Association of Immunologists
Authors (28)
Stanley Dinko
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Candie Joly
Paul Mazet
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Gaëlle Sandillon
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Victor Magneron
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Natalia Nunez
Life and Soft, A SeqOne Company, Montpellier, France
Céline Mayet
Life and Soft, A SeqOne Company, Montpellier, France
Ségolène Diry
Life and Soft, A SeqOne Company, Montpellier, France
Cassandra Gaspar
Life and Soft, A SeqOne Company, Montpellier, France
Marco Leonec
Sophie Luccantoni
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Camille Ludot
Benoit Delache
Emma Jougla
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Julie Morin
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Wafa Zouaoui-Frigui
Unit for Integrated Mycobacterial Pathogenomics, Institut Pasteur, Université Paris Cité , Paris,
Roland Brosch
Institut Pasteur, Université Paris Cité, Unit for Integrated Mycobacterial Pathogenomics, CNRS UMR 6047, Microbiology Department
Vanessa Contreras
Anne-Sophie Gallouët
Nathalie Bosquet
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Francis Relouzat
Quentin Pascal
Baptiste Jean
1CHU de Lyon, Lyon, France
Marion Holzapfel
Immune Diseases, Microbiology and Innovative Therapies (IDMIT/UMRS1184), Université Paris-Saclay – Inserm - CEA, Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Olivier Lambotte
Thibaut Naninck
Roger Le Grand
Julien Lemaitre