tetano
Editor, Senior Moderator
Am J Physiol Lung Cell Mol Physiol. 2017 Apr 13:ajplung.00075.2017. doi: 10.1152/ajplung.00075.2017. [Epub ahead of print]
[h=1]Immunomodulators Targeting MARCO Expression Improve Resistance to Post-influenza Bacterial Pneumonia.[/h] Wu M, Gibbons JG, Deloid GM[SUP]1[/SUP], Bedugnis AS, Thimmulappa RK[SUP]2[/SUP], Biswal S[SUP]3[/SUP], Kobzik L[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Down-regulation of the alveolar macrophage (AM) macrophage receptor with collagenous structure (MARCO) leads to susceptibility to post-influenza 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 of 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 IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells, and improved survival in mice with post-influenza 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 IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in post-influenza bacterial pneumonia.
Copyright ? 2017, American Journal of Physiology-Lung Cellular and Molecular Physiology.
[h=4]KEYWORDS:[/h] MARCO; immunomodulators; influenza; scavenger receptors; secondary pneumonia
PMID: 28408365 DOI: 10.1152/ajplung.00075.2017
[h=1]Immunomodulators Targeting MARCO Expression Improve Resistance to Post-influenza Bacterial Pneumonia.[/h] Wu M, Gibbons JG, Deloid GM[SUP]1[/SUP], Bedugnis AS, Thimmulappa RK[SUP]2[/SUP], Biswal S[SUP]3[/SUP], Kobzik L[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Down-regulation of the alveolar macrophage (AM) macrophage receptor with collagenous structure (MARCO) leads to susceptibility to post-influenza 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 of 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 IFNγ to model influenza effects. Activators of Nrf2 (sulforaphane) or Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in phagocytosis in IFNγ-treated cells, and improved survival in mice with post-influenza 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 IFNγ-treated AM-MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling or Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in post-influenza bacterial pneumonia.
Copyright ? 2017, American Journal of Physiology-Lung Cellular and Molecular Physiology.
[h=4]KEYWORDS:[/h] MARCO; immunomodulators; influenza; scavenger receptors; secondary pneumonia
PMID: 28408365 DOI: 10.1152/ajplung.00075.2017