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HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection.
Yang, Baojun; Mukherjee, Tanmoy; Radhakrishnan, Rajesh; Paidipally, Padmaja; Ansari, Danish; John, Sahana; Vankayalapati, Ramakrishna; Tripathi, Deepak; Yi, Guohua.
Afiliación
  • Yang B; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA.
  • Mukherjee T; Center for Biomedical Research, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA.
  • Radhakrishnan R; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
  • Paidipally P; Center for Biomedical Research, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA.
  • Ansari D; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
  • John S; Center for Biomedical Research, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA.
  • Vankayalapati R; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
  • Tripathi D; Center for Biomedical Research, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA.
  • Yi G; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.
Int J Mol Sci ; 24(8)2023 Apr 14.
Article en En | MEDLINE | ID: mdl-37108430
Mycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and caused ~1.6 million deaths in 2021. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared with HIV- LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Plasma samples collected from healthy and HIV-infected individuals were investigated using liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using the online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, and quantitative reverse-transcription PCR (qRT-PCR) were performed using standard procedures to determine the surface markers, cytokines, and other signaling molecule expressions. Seahorse extra-cellular flux assays were used to measure mitochondrial oxidative phosphorylation and glycolysis. Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared with healthy donors. One of the HIV-upregulated metabolites, N-acetyl-L-alanine (ALA), inhibits pro-inflammatory cytokine IFN-γ production by the NK cells of LTBI+ individuals. ALA inhibits the glycolysis of LTBI+ individuals' NK cells in response to Mtb. Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK-cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV-Mtb interaction and providing insights into the implication of nutrition intervention and therapy for HIV-Mtb co-infected patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Infecciones por VIH / Mycobacterium tuberculosis Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Infecciones por VIH / Mycobacterium tuberculosis Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza