| First Author | Wu M | Year | 2017 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 313 |
| Issue | 1 | Pages | L138-L153 |
| PubMed ID | 28408365 | Mgi Jnum | J:243298 |
| Mgi Id | MGI:5908067 | Doi | 10.1152/ajplung.00075.2017 |
| Citation | Wu M, et al. (2017) Immunomodulators targeting MARCO expression improve resistance to postinfluenza bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol 313(1):L138-L153 |
| abstractText | Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNgamma to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNgamma-treated cells and improved survival in mice with postinfluenza pneumococcal pneumonia. Transcription factor analysis also indicated a role for transcription factor E-box (TFEB) in MARCO recovery. Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The ability of Akt activation to increase MARCO expression in IFNgamma-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia. |
