| First Author | Shepard RM | Year | 2024 |
| Journal | Sci Transl Med | Volume | 16 |
| Issue | 754 | Pages | eadi6887 |
| PubMed ID | 38959328 | Mgi Jnum | J:351126 |
| Mgi Id | MGI:7663939 | Doi | 10.1126/scitranslmed.adi6887 |
| Citation | Shepard RM, et al. (2024) PI3Kgamma inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections. Sci Transl Med 16(754):eadi6887 |
| abstractText | Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kgamma), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kgamma deletion and inhibition with the clinical PI3Kgamma inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kgamma in inflammatory lung disease and support the potential use of PI3Kgamma inhibitors to suppress inflammation in severe infectious diseases. |
