tetano
Editor, Senior Moderator
Sci Transl Med
. 2024 Jul 3;16(754):eadi6887.
doi: 10.1126/scitranslmed.adi6887. Epub 2024 Jul 3. PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections
Ryan M Shepard[SUP] 1 [/SUP], Anghesom Ghebremedhin[SUP] 1 [/SUP], Isaraphorn Pratumchai[SUP] 2 [/SUP], Sally R Robinson[SUP] 3 4 [/SUP], Courtney Betts[SUP] 5 [/SUP], Jingjing Hu[SUP] 6 [/SUP], Roman Sasik[SUP] 7 [/SUP], Kathleen M Fisch[SUP] 7 8 [/SUP], Jaroslav Zak[SUP] 2 [/SUP], Hui Chen[SUP] 1 [/SUP], Marc Paradise[SUP] 1 [/SUP], Jason Rivera[SUP] 1 [/SUP], Mohammad Amjad[SUP] 1 [/SUP], Satoshi Uchiyama[SUP] 9 [/SUP], Hideya Seo[SUP] 9 [/SUP], Alejandro D Campos[SUP] 6 [/SUP], Denise Ann Dayao[SUP] 3 [/SUP], Saul Tzipori[SUP] 3 [/SUP], Cesar Piedra-Mora[SUP] 10 [/SUP], Soumita Das[SUP] 6 [/SUP], Farnaz Hasteh[SUP] 6 [/SUP], Hana Russo[SUP] 6 [/SUP], Xin Sun[SUP] 9 [/SUP], Le Xu[SUP] 9 [/SUP], Laura Crotty E Alexander[SUP] 11 [/SUP], Jason M Duran[SUP] 11 [/SUP], Mazen Odish[SUP] 11 [/SUP], Victor Pretorius[SUP] 12 [/SUP], Nell C Kirchberger[SUP] 5 [/SUP], Shao-Ming Chin[SUP] 1 [/SUP], Tami Von Schalscha[SUP] 6 [/SUP], David Cheresh[SUP] 6 [/SUP], John D Morrey[SUP] 13 [/SUP], Rossitza Alargova[SUP] 14 [/SUP], Brenda O'Connell[SUP] 14 [/SUP], Theodore A Martinot[SUP] 14 [/SUP], Sandip P Patel[SUP] 15 [/SUP], Victor Nizet[SUP] 9 16 [/SUP], Amanda J Martinot[SUP] 3 4 10 [/SUP], Lisa M Coussens[SUP] 5 17 [/SUP], John R Teijaro[SUP] 2 [/SUP], Judith A Varner[SUP] 1 6 [/SUP]
Affiliations
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 (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ 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 PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.
. 2024 Jul 3;16(754):eadi6887.
doi: 10.1126/scitranslmed.adi6887. Epub 2024 Jul 3. PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections
Ryan M Shepard[SUP] 1 [/SUP], Anghesom Ghebremedhin[SUP] 1 [/SUP], Isaraphorn Pratumchai[SUP] 2 [/SUP], Sally R Robinson[SUP] 3 4 [/SUP], Courtney Betts[SUP] 5 [/SUP], Jingjing Hu[SUP] 6 [/SUP], Roman Sasik[SUP] 7 [/SUP], Kathleen M Fisch[SUP] 7 8 [/SUP], Jaroslav Zak[SUP] 2 [/SUP], Hui Chen[SUP] 1 [/SUP], Marc Paradise[SUP] 1 [/SUP], Jason Rivera[SUP] 1 [/SUP], Mohammad Amjad[SUP] 1 [/SUP], Satoshi Uchiyama[SUP] 9 [/SUP], Hideya Seo[SUP] 9 [/SUP], Alejandro D Campos[SUP] 6 [/SUP], Denise Ann Dayao[SUP] 3 [/SUP], Saul Tzipori[SUP] 3 [/SUP], Cesar Piedra-Mora[SUP] 10 [/SUP], Soumita Das[SUP] 6 [/SUP], Farnaz Hasteh[SUP] 6 [/SUP], Hana Russo[SUP] 6 [/SUP], Xin Sun[SUP] 9 [/SUP], Le Xu[SUP] 9 [/SUP], Laura Crotty E Alexander[SUP] 11 [/SUP], Jason M Duran[SUP] 11 [/SUP], Mazen Odish[SUP] 11 [/SUP], Victor Pretorius[SUP] 12 [/SUP], Nell C Kirchberger[SUP] 5 [/SUP], Shao-Ming Chin[SUP] 1 [/SUP], Tami Von Schalscha[SUP] 6 [/SUP], David Cheresh[SUP] 6 [/SUP], John D Morrey[SUP] 13 [/SUP], Rossitza Alargova[SUP] 14 [/SUP], Brenda O'Connell[SUP] 14 [/SUP], Theodore A Martinot[SUP] 14 [/SUP], Sandip P Patel[SUP] 15 [/SUP], Victor Nizet[SUP] 9 16 [/SUP], Amanda J Martinot[SUP] 3 4 10 [/SUP], Lisa M Coussens[SUP] 5 17 [/SUP], John R Teijaro[SUP] 2 [/SUP], Judith A Varner[SUP] 1 6 [/SUP]
Affiliations
- PMID: 38959328
- DOI: 10.1126/scitranslmed.adi6887
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 (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ 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 PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.