Open AccessAirway delivery of interferon‐ γ overexpressing macrophages confers resistance to Mycobacterium avium infection in SCID mice
Author(s) -
Pasula Rajamouli,
Britigan Bradley E.,
Kesavalu Banurekha,
Abdalla Maher Y.,
Martin William J.
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13008
Subject(s) - macrophage , immunology , lung , interferon gamma , microbiology and biotechnology , immune system , interferon , in vitro , medicine , alveolar macrophage , biology , biochemistry
Mycobacterium avium ( M. avium ) causes significant pulmonary infection, especially in immunocompromised hosts. Alveolar macrophages ( AM s) represent the first line of host defense against infection in the lung. Interferon gamma ( IFN ‐ γ ) activation of AM s enhances in vitro killing of pathogens such as M. avium . We hypothesized that airway delivery of AM s into the lungs of immunodeficient mice infected with M. avium will inhibit M. avium growth in the lung and that this macrophage function is in part IFN ‐ γ dependent. In this study, normal BALB /c and BALB /c SCID mice received M. avium intratracheally while on mechanical ventilation. After 30 days, M. avium numbers increased in a concentration‐dependent manner in SCID mice compared with normal BALB /c mice. Airway delivery of IFN ‐ γ ‐activated BALB /c AM s or J774A.1 macrophages overexpressing IFN ‐ γ into the lungs of SCID mice resulted in a significant decrease in M. avium growth ( P < 0.01, both comparisons) and limited dissemination to other organs. In addition, airway delivery of IFN ‐ γ activated AM s and macrophages overexpressing IFN ‐ γ increased the levels of IFN ‐ γ and TNF ‐ α in SCID mice. A similar protective effect against M. avium infection using J774A.1 macrophages overexpressing IFN ‐ γ was observed in IFN ‐ γ knockout mice. These data suggest that administration of IFN ‐ γ activated AM s or macrophages overexpressing IFN ‐ γ may partially restore local alveolar host defense against infections like M. avium , even in the presence of ongoing systemic immunosuppression.