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Dysregulation of the PI3k signaling cascade can constitutively activate growth pathways to trigger the progression of cancer, resulting in the development of multiple inhibitors as cancer therapeutics. Objectives: The wide array of cells expressing PI3k also include immune cells, and the inhibition of these receptors has shown promise in combating inflammation and infectious disease, a relationship we sought to examine further. Methods: We infected wild-type and PI3k\u03b3 knockout murine macrophages as well as PI3k\u03b3 inhibitor-treated THP-1 human macrophage-like cells with Staphylococcus aureus and quantified inflammation through gene expression analysis, protein secretion assays, and immunofluorescence imaging. Results: We observed that knockout of PI3k\u03b3 in murine macrophages alongside pharmacological inhibition through IPI549 treatment in THP-1 cells led to an NF-\u03baB-driven suppression in transcription and release of inflammatory cytokines upon infection with methicillin-resistant Staphylococcus aureus. We were also able to confirm that this suppression of NF-\u03baB translocation and subsequent decrease in inflammatory cytokine release did not compromise and even slightly boosted the bacterial killing ability. Conclusion: PI3k is primarily targeted for cancer therapies, but further exploration can also be carried out on its potential roles in treating bacterial infection.<\/jats:p>","DOI":"10.3390\/antibiotics14030315","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T06:02:40Z","timestamp":1742277760000},"page":"315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of PI3k-Gamma Modulation in Bacterial Infection: A Review of the Literature and Selected Experimental Observations"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-6045","authenticated-orcid":false,"given":"Daniel","family":"Sun","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Pediatrics, UC San Diego, La Jolla, CA 92093, USA"},{"name":"Biomedical Sciences Graduate Program, UC San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8208-8995","authenticated-orcid":false,"given":"Alexandria","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UC San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-4671","authenticated-orcid":false,"given":"Fatemeh","family":"Askarian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UC San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2747-7699","authenticated-orcid":false,"given":"Elisabet","family":"Bj\u00e5nes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UC San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1134-7782","authenticated-orcid":false,"given":"Eric X.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UC San Diego, La Jolla, CA 92093, USA"},{"name":"Biomedical Sciences Graduate Program, UC San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9251-0600","authenticated-orcid":false,"given":"Judith","family":"Varner","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, UC San Diego, La Jolla, CA 92093, USA"},{"name":"Moores Cancer Center, UC San Diego, La Jolla 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3847-0422","authenticated-orcid":false,"given":"Victor","family":"Nizet","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Pediatrics, UC San Diego, La Jolla, CA 92093, USA"},{"name":"Biomedical Sciences Graduate Program, UC San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/S1470-2045(23)00182-1","article-title":"Global Funding for Cancer Research between 2016 and 2020: A Content Analysis of Public and Philanthropic Investments","volume":"24","author":"McIntosh","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12943-019-0954-x","article-title":"Targeting PI3K in Cancer: Mechanisms and Advances in Clinical Trials","volume":"18","author":"Yang","year":"2019","journal-title":"Mol. 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