{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:36:28Z","timestamp":1789140988329,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, Texas, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is now widely accepted that NK cells can acquire memory, and this makes them more effective to protect against some pathogens. Prior reports indicate memory-like NK cells (mlNKs) in murine model of Mycobacterium tuberculosis (Mtb) as well as in healthy individuals with latent TB infection (LTBI). The increased expression of CD226 was evident in mlNKs from LTBI+ people after stimulation with \u03b3-irradiated Mtb (\u03b3-Mtb). We thus evaluated the contribution of costimulatory CD226 signaling in the functionality of mlNKs in LTBI+ people. We found that blockade of CD226 signaling using the antibody- or CRISPR\/Cas9-mediated deletion of the CD226 gene in NK cells diminished the proliferation of mlNKs from LTBI+ people. Blocking CD226 signaling also reduced the phosphorylation of FOXO1 and cMyc expression. Additionally, cMyc inhibition using a chemical inhibitor reduced proliferation by mlNKs from LTBI+ people. Moreover, blocking CD226 signaling reduced glycolysis in NK cells, and the inhibition of glycolysis led to reduced effector function of mlNKs from LTBI+ people. Overall, our results provide a role for CD226 signaling in mlNK responses to Mtb.<\/jats:p>","DOI":"10.3390\/ijms232112838","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T22:00:27Z","timestamp":1666735227000},"page":"12838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Costimulatory CD226 Signaling Regulates Proliferation of Memory-like NK Cells in Healthy Individuals with Latent Mycobacterium tuberculosis Infection"],"prefix":"10.3390","volume":"23","author":[{"given":"Oscar","family":"Murillo","sequence":"first","affiliation":[{"name":"Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josimar Dornelas","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weshely","family":"Kujur","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Velasco-Alzate","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Sen Santara","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagarjun V.","family":"Konduru","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Mulik","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJM198906293202605","article-title":"Severe Herpesvirus Infections in an Adolescent without Natural Killer Cells","volume":"320","author":"Biron","year":"1989","journal-title":"N. 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