SPHK2-Generated S1P in CD11b+ Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages

Research output: Contribution to journalArticle

Authors

  • Jagdish C. Joshi
  • Bhagwati Joshi
  • Ian Rochford
  • Sheikh Rayees
  • Md Zahid Akhter
  • Sukriti Baweja
  • Koteshwara Rao Chava
  • Mohammad Tauseef
  • Hazem Abdelkarim
  • Viswanathan Natarajan
  • Vadim Gaponenko
  • Dolly Mehta

External Institution(s)

  • University of Illinois at Chicago

Details

Original languageEnglish (US)
Pages (from-to)4096-4109.e5
JournalCell reports
Volume30
Issue number12
StatusPublished - Mar 24 2020
Peer-reviewedYes

Abstract

Acute lung injury (ALI) is a lethal inflammatory lung disorder whose incidence is on the rise. Alveolar macrophages normally act to resolve inflammation, but when dysregulated they can provoke ALI. We demonstrate that monocyte-derived macrophages (CD11b+ macrophages) recruited into the airspace upregulate the anti-inflammatory function of alveolar macrophages by suppressing their stimulator of type 1 interferon gene (STING) signaling. Depletion of CD11b+ macrophages in mice (macrophagedep mice) after endotoxin or after Pseudomonas aeruginosa causes expansion of the inflammatory alveolar macrophage population, leading to neutrophil accumulation, irreversible loss of lung vascular barrier function, and lethality. We show that CD11b+ macrophages suppress alveolar macrophage-STING signaling via sphingosine kinase-2 (SPHK2) generation of sphingosine-1-phosphate (S1P). Thus, adoptive transfer of wild-type (WT) or STING−/−, but not SPHK2−/−, CD11b monocytes from murine bone marrow into injured macrophagedep mice rescue anti-inflammatory alveolar macrophages and reverse lung vascular injury. SPHK2-induced S1P generation in CD11b+ macrophages has the potential to educate alveolar macrophages to resolve ALI.

    Research areas

  • CD11b+ macrophages, S1P, acute lung injury, alveolar macrophages, cGAMP, inflammation, recruited macrophages, sphingosine kinase 2, sting

Citation formats

APA

Joshi, J. C., Joshi, B., Rochford, I., Rayees, S., Akhter, M. Z., Baweja, S., ... Mehta, D. (2020). SPHK2-Generated S1P in CD11b+ Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages. Cell reports, 30(12), 4096-4109.e5. https://doi.org/10.1016/j.celrep.2020.02.112

Harvard

Joshi, JC, Joshi, B, Rochford, I, Rayees, S, Akhter, MZ, Baweja, S, Chava, KR, Tauseef, M, Abdelkarim, H, Natarajan, V, Gaponenko, V & Mehta, D 2020, 'SPHK2-Generated S1P in CD11b+ Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages', Cell reports, vol. 30, no. 12, pp. 4096-4109.e5. https://doi.org/10.1016/j.celrep.2020.02.112