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Upon infection,\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              (\n              <jats:italic>M.tb<\/jats:italic>\n              ) is deposited in the alveoli and encounters the lung mucosa or alveolar lining fluid (ALF). We previously showed that, as we age, ALF presents a higher degree of oxidation and inflammatory mediators, which favors\n              <jats:italic>M.tb<\/jats:italic>\n              replication in human macrophages and alveolar epithelial cells (ATs). Here, we define the transcriptional profile of\n              <jats:italic>M.tb<\/jats:italic>\n              when exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) humans before and during infection of ATs. Prior to infection,\n              <jats:italic>M.tb<\/jats:italic>\n              exposure to E-ALF upregulated genes essential for bacterial host adaptation directly involved in\n              <jats:italic>M.tb<\/jats:italic>\n              pathogenesis. During infection of ATs, E-ALF exposed\n              <jats:italic>M.tb<\/jats:italic>\n              further upregulated genes involved in its ability to escape into the AT cytosol bypassing critical host defense mechanisms, as well as genes associated with defense against oxidative stress. These findings demonstrate how alterations in human ALF during the aging process can impact the metabolic status of\n              <jats:italic>M.tb<\/jats:italic>\n              , potentially enabling a greater adaptation and survival within host cells. Importantly, we present the first transcriptomic analysis on the impact of the elderly lung mucosa on\n              <jats:italic>M.tb<\/jats:italic>\n              pathogenesis during intracellular replication in ATs.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Tuberculosis is one of the leading causes of death due to a single infectious agent. Upon infection,\n                <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                (\n                <jats:italic>M.tb<\/jats:italic>\n                ) is deposited in the alveoli and comes in contact with the alveolar lining fluid (ALF). We previously showed that elderly ALF favors\n                <jats:italic>M.tb<\/jats:italic>\n                replication in human macrophages and alveolar epithelial cells (ATs). Here we define the transcriptional profile of when exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) humans before and during infection of ATs. Prior to infection, exposure to E-ALF upregulates genes essential for bacterial host adaptation and pathogenesis. During infection of ATs, E-ALF further upregulates\n                <jats:italic>M.tb<\/jats:italic>\n                genes involved in its ability to escape into the AT cytosol, as well as genes for defense against oxidative stress. These findings demonstrate how alterations in human ALF during the aging process can impact the metabolic status of\n                <jats:italic>M.tb<\/jats:italic>\n                , potentially enabling a greater adaptation and survival within host cells.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01790-24","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T14:00:28Z","timestamp":1731074428000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Impact of the elderly lung mucosa on\n            <i>Mycobacterium tuberculosis<\/i>\n            transcriptional adaptation during infection of alveolar epithelial cells"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-9714","authenticated-orcid":false,"given":"Ang\u00e9lica M.","family":"Olmo-Font\u00e1nez","sequence":"first","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]},{"name":"Integrated Biomedical Sciences Program, University of Texas Health Science Center at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1941-2545","authenticated-orcid":false,"given":"Anna","family":"Allu\u00e9-Guardia","sequence":"additional","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]},{"name":"International Center for the Advancement of Research & Education (I \u2022 CARE), Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-8718","authenticated-orcid":false,"given":"Andreu","family":"Garcia-Vilanova","sequence":"additional","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Glenn","sequence":"additional","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Infectious Disease Division, The Ohio State University","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Merritt","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Ohio State University","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry S.","family":"Schlesinger","sequence":"additional","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]},{"name":"International Center for the Advancement of Research & Education (I \u2022 CARE), Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Turner","sequence":"additional","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]},{"name":"International Center for the Advancement of Research & Education (I \u2022 CARE), Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-5941","authenticated-orcid":true,"given":"Jordi B.","family":"Torrelles","sequence":"additional","affiliation":[{"name":"Population Health and Host-Pathogen Interactions Programs, Texas Biomedical Research Institute","place":["San Antonio, USA"]},{"name":"International Center for the Advancement of Research & Education (I \u2022 CARE), Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","volume-title":"Ageing and health","author":"WHO","year":"2022","unstructured":"WHO. 2022. 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