PI3Kg inhibition circumvents inflammation and mortality in SARS-CoV-2 and other infections

Virulent infectious agents such as SARS-CoV-2 and Methicillin Resistant Staphylococcus Aureus (MRSA) induce tissue damage that recruits neutrophils and monocyte/macrophages that promote T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils and macrophages recruited to pathogen infected lungs, including SARS-CoV-2 infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kg), a signaling protein that coordinately controls granulocyte and monocyte trafficking to diseased tissues and immune suppressive, pro-fibrotic transcription in myeloid cells. PI3Kg deletion and inhibition with the clinical PI3Kg 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 PI3Kg in inflammatory lung disease and support the potential use of PI3Kg inhibitors to suppress inflammation ..., Human subjects
All human tissue analyses were conducted on de-identified tissue under guidelines established by the Institutional Review Board for human subject research of the University of California, San Diego. Postmortem tissue studies received IRB exemption from oversight as research on deceased patients is not classified as human subjects research by the US Department of Health and Human Services or the US Food and Drug Administration. All patients in this study were admitted early in the pandemic during the first 3-6 months after the first cases of COVID-19 were reported in the US when no specific therapeutics had been developed. De-identified lung tissue was obtained upon rapid autopsy of deceased COVID-19 patients formalin-fixed for 48h and processed by the Department of Pathology, UCSD, into paraffin-embedded tissue blocks by the Moores Cancer Center histology shared resource, UCSD, San Diego, CA. Normal human lung tissue was obtained from consented patients during lung cancer..., Any spreadsheet program such as Excel., # PI3Kg inhibition circumvents inflammation and mortality in SARS-CoV-2 and other infections

* File name: README_Dataset-PI3KgCOVIDproject.txt

* Authors: Judith A. Varner

* Other contributors: Ryan M. Shepard, Anghesom Ghebremedhin, Isa Pratumchai, Sally Robinson, Courtney Betts, Jingjing Hu, Roman Sasik, Kathleen M. Fisch, Jaroslav Zak, Hui Chen, Marc Paradise, Mohammad Amjad, Jason Rivera, Satoshi Uchiyama, Hideya Seo, Alex Campos, Denise Ann Dayao, Saul Tzipori, Cesar Piedra-Mora, Soumita Das, Farnaz Hasteh, Hana Russo, Xin Sun, Le Xu, Laura Crotty Alexander, Jason M. Duran, Mazen Odish, Victor Pretorius, Nell C. Kirchberger, Shao-ming Chin, Tami Von Schalscha, David Cheresh, John D. Morrey, Rossitza Alargova, Brenda O’Connell, Theodore A. Martinot, Sandip P. Patel, Victor Nizet, Amanda J. Martinot, Lisa M. Coussens, John Teijaro

* Date created: 2024-03-14

## Dataset Version and Release History

* Current Version:
* Number: 1.0.0
* Date: 2024-03-14
*...