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Ecto-5′-Nucleotidase (CD73) Deficiency in Mycobacterium tuberculosis-Infected Mice Enhances Neutrophil Recruitment

Abstract : ABSTRACT The immune system needs safeguards that prevent collateral tissue damage mediated by the immune system while enabling an effective response against a pathogen. The purinergic pathway is one such mechanism and finely modulates inflammation by sensing nucleotides in the environment. Extracellular ATP is considered to be a danger signal leading to a proinflammatory response, whereas adenosine is immunosuppressive. CD73, also called ecto-5′-nucleotidase, occupies a strategic position in this pathway, as it is the main enzyme responsible for the generation of adenosine from ATP. Here, we explore the role of CD73 during tuberculosis, a disease characterized by an immune response that is harmful to the host and unable to eradicate Mycobacterium tuberculosis . Using CD73 knockout (KO) mice, we found that CD73 regulates the response to M. tuberculosis infection in vitro and in vivo . Mycobacterium-infected murine macrophages derived from CD73 KO mice secrete more keratinocyte chemoattractant (KC), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) and release less vascular endothelial growth factor (VEGF) upon ATP stimulation than do those derived from wild-type (WT) mice. In vivo , CD73 limits the early influx of neutrophils to the lungs without affecting bacterial growth and dissemination. Collectively, our results support the view that CD73 fine-tunes antimycobacterial immune responses.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03525488
Contributor : Ludovic Tailleux Connect in order to contact the contributor
Submitted on : Thursday, January 13, 2022 - 9:47:10 PM
Last modification on : Sunday, January 16, 2022 - 3:07:05 AM

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Laetitia Petit-Jentreau, Grégory Jouvion, Patricia Charles, Laleh Majlessi, Brigitte Gicquel, et al.. Ecto-5′-Nucleotidase (CD73) Deficiency in Mycobacterium tuberculosis-Infected Mice Enhances Neutrophil Recruitment. Infection and Immunity, American Society for Microbiology, 2015, 83 (9), pp.3666-3674. ⟨10.1128/IAI.00418-15⟩. ⟨pasteur-03525488⟩

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