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Alveolar macrophages (AM<\/jats:styled-content>s) represent the first line of host defense against infection in the lung. Interferon gamma (IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic>) activation of AM<\/jats:styled-content>s enhances in\u00a0vitro killing of pathogens such as M. avium<\/jats:italic>. We hypothesized that airway delivery of AM<\/jats:styled-content>s into the lungs of immunodeficient mice infected with M. avium<\/jats:italic> will inhibit M. avium<\/jats:italic> growth in the lung and that this macrophage function is in part IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> dependent. In this study, normal BALB<\/jats:styled-content>\/c and BALB<\/jats:styled-content>\/c SCID<\/jats:styled-content> mice received M. avium<\/jats:italic> intratracheally while on mechanical ventilation. After 30\u00a0days, M. avium<\/jats:italic> numbers increased in a concentration\u2010dependent manner in SCID<\/jats:styled-content> mice compared with normal BALB<\/jats:styled-content>\/c mice. Airway delivery of IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic>\u2010activated BALB<\/jats:styled-content>\/c AM<\/jats:styled-content>s or J774A.1 macrophages overexpressing IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> into the lungs of SCID<\/jats:styled-content> mice resulted in a significant decrease in M. avium<\/jats:italic> growth (P<\/jats:italic>\u00a0<\u00a00.01, both comparisons) and limited dissemination to other organs. In addition, airway delivery of IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> activated AM<\/jats:styled-content>s and macrophages overexpressing IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> increased the levels of IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> and TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> in SCID<\/jats:styled-content> mice. A similar protective effect against M. avium<\/jats:italic> infection using J774A.1 macrophages overexpressing IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> was observed in IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> knockout mice. These data suggest that administration of IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> activated AM<\/jats:styled-content>s or macrophages overexpressing IFN<\/jats:styled-content>\u2010\u03b3<\/jats:italic> may partially restore local alveolar host defense against infections like M. avium<\/jats:italic>, even in the presence of ongoing systemic immunosuppression.<\/jats:p>","DOI":"10.14814\/phy2.13008","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T02:30:42Z","timestamp":1479436242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Airway delivery of interferon\u2010\u03b3<\/i> overexpressing macrophages confers resistance to Mycobacterium avium<\/i> infection in SCID<\/scp> mice"],"prefix":"10.14814","volume":"4","author":[{"given":"Rajamouli","family":"Pasula","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Cincinnati College of Medicine Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley E.","family":"Britigan","sequence":"additional","affiliation":[{"name":"Research Service VA Medical Center \u2013 Nebraska\/Western Iowa Omaha Nebraska"},{"name":"Department of Internal Medicine and Microbiology and Immunology University of Nebraska Medical Center Omaha Nebraska"},{"name":"Department of Pathology and Microbiology College of Medicine University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banurekha","family":"Kesavalu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Cincinnati College of Medicine Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maher Y.","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Research Service VA Medical Center \u2013 Nebraska\/Western Iowa Omaha Nebraska"},{"name":"Department of Pathology and Microbiology College of Medicine University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"William J.","family":"Martin","sequence":"additional","affiliation":[{"name":"College of Public Health The Ohio State University Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,17]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"352","article-title":"Effector mechanisms involved in cytokine\u2010mediated bacteriostasis of Mycobacterium avium infections in murine macrophages","volume":"80","author":"Appelberg R.","year":"1993","journal-title":"Immunology"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1128\/iai.62.9.3962-3971.1994","article-title":"Role of gamma interferon and tumor necrosis factor alpha during T\u2010cell\u2010independent and \u2010dependent phases of Mycobacterium avium infection","volume":"69","author":"Appelberg R.","year":"1994","journal-title":"Infect. 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