SPHK2-Generated S1P in CD11b+ Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages
| Autor: | Sukriti Baweja, Zahid Akhter, Koteshwara Rao Chava, Ian Rochford, Hazem Abdelkarim, Jagdish Chandra Joshi, Mohammad Tauseef, Dolly Mehta, Viswanathan Natarajan, Sheikh Rayees, Vadim Gaponenko, Bhagwati Joshi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Population Inflammation Lung injury General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medicine education lcsh:QH301-705.5 education.field_of_study Lung biology Sphingosine business.industry respiratory system 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Integrin alpha M chemistry Immunology Alveolar macrophage biology.protein medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 30, Iss 12, Pp 4096-4109.e5 (2020) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2020.02.112 |
| Popis: | Summary: 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. : Joshi et al. demonstrate an essential role of SPHK2+ monocyte-derived CD11b+ macrophages, which are recruited to the airspace, in promoting anti-inflammatory function of alveolar macrophages during lung injury. They show that S1P generated by recruited SPHK2+-CD11b+ macrophages suppresses STING signaling in alveolar macrophages to resolve inflammatory injury. Keywords: acute lung injury, sting, sphingosine kinase 2, alveolar macrophages, recruited macrophages, CD11b+ macrophages, S1P, inflammation, cGAMP |
| Databáze: | OpenAIRE |
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