{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:26:55Z","timestamp":1788848815763,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR073665"],"award-info":[{"award-number":["R01AR073665"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI111205 , R01AI146177"],"award-info":[{"award-number":["R01AI111205 , R01AI146177"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is a leading cause of bacteremia, further complicated by the emergence of antibiotic-resistant strains such as methicillin-resistant <jats:italic>S. aureus<\/jats:italic> (MRSA). A better understanding of host defense mechanisms is needed for the development of host-directed therapies as an alternative approach to antibiotics. The levels of IL-1, IL-17, and TNF-\u03b1 cytokines in circulation have been associated with predictive outcomes in patients with <jats:italic>S. aureus<\/jats:italic> bacteremia. However, their causative role in survival and the cell types involved in these responses during bacteremia is not entirely clear. Using a mouse model of <jats:italic>S. aureus<\/jats:italic> bacteremia, we demonstrated that IL-17A\/F and TNF-\u03b1 had no significant impact on survival, whereas IL-1R signaling was critical for survival during <jats:italic>S. aureus<\/jats:italic> bacteremia. Furthermore, we identified that T cells, but not neutrophils, monocytes\/macrophages, or endothelial cells were the crucial cell type for IL-1R-mediated survival against <jats:italic>S. aureus<\/jats:italic> bacteremia. Finally, we determined that the expression of IL-1R on \u03b3\u03b4 T cell, but not CD4<jats:sup>+<\/jats:sup> or CD8<jats:sup>+<\/jats:sup> T cells was responsible for survival against the <jats:italic>S. aureus<\/jats:italic> bacteremia. Taken together, we uncovered a role for IL-1R, but not IL-17A\/F and TNF-\u03b1 in protection against <jats:italic>S. aureus<\/jats:italic> bacteremia. Importantly, \u03b3\u03b4 T cell-intrinsic expression of IL-1R was crucial for survival, but not on other immune cells or endothelial cells. These findings reveal potential cellular and immunological targets for host-directed therapies for improved outcomes against <jats:italic>S. aureus<\/jats:italic> bacteremia.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1171934","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T13:15:42Z","timestamp":1688735742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["\u03b3\u03b4 T cell-intrinsic IL-1R promotes survival during Staphylococcus aureus bacteremia"],"prefix":"10.3389","volume":"14","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Z.","family":"Ahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin A.","family":"Dikeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Youn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan K.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/ice.2019.296","article-title":"Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: summary of data reported to the national healthcare safety network, 2015-2017","volume":"41","author":"Weiner-Lastinger","year":"2020","journal-title":"Infect Control Hosp Epidemiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.amjmed.2022.09.017","article-title":"The golden grapes of wrath - staphylococcus aureus bacteremia: a clinical review","volume":"136","author":"Lam","year":"2023","journal-title":"Am J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0069-2019","article-title":"Immunity to staphylococcus aureus: implications for vaccine development","volume":"7","author":"Proctor","year":"2019","journal-title":"Immun to. Microbiol Spectr"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.3010","article-title":"Effect of an investigational vaccine for preventing staphylococcus aureus infections after cardiothoracic surgery: a randomized trial","volume":"309","author":"Fowler","year":"2013","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24608","article-title":"IL-1\u03b2 and TNF are essential in controlling an experimental orthopaedic implant associated infection","volume":"38","author":"Wang","year":"2020","journal-title":"J Orthop Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40891","article-title":"IL-17 is essential for host defense against cutaneous staphylococcus aureus infection in mice","volume":"120","author":"Cho","year":"2010","journal-title":"J Clin Invest"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818256116","article-title":"Clonal Vgamma6+Vdelta4+ T cells promote IL-17-mediated immunity against staphylococcus aureus skin infection","volume":"116","author":"Marchitto","year":"2019","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.immuni.2005.11.011","article-title":"MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against staphylococcus aureus","volume":"24","author":"Miller","year":"2006","journal-title":"Immunity"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuz030","article-title":"Development of a vaccine against staphylococcus aureus invasive infections: evidence based on human immunity, genetics and bacterial evasion mechanisms","volume":"44","author":"Miller","year":"2020","journal-title":"FEMS Microbiol Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4161\/hv.34407","article-title":"Mortality among recipients of the Merck V710 staphylococcus aureus vaccine after postoperative s. aureus infections: an analysis of possible contributing host factors","volume":"10","author":"McNeely","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis552","article-title":"Elevated serum interleukin-10 at time of hospital admission is predictive of mortality in patients with staphylococcus aureus bacteremia","volume":"206","author":"Rose","year":"2012","journal-title":"J Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001465","article-title":"A dysregulated balance of proinflammatory and anti-inflammatory host cytokine response early during therapy predicts persistence and mortality in staphylococcus aureus bacteremia","volume":"44","author":"Minejima","year":"2016","journal-title":"Crit Care Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.jaci.2016.07.001","article-title":"IL-22 derived from \u03b3\u03b4 T cells restricts staphylococcus aureus infection of mechanically injured skin","volume":"138","author":"Malhotra","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"6774","DOI":"10.1038\/s41598-019-42919-y","article-title":"Comparison of livestock-associated and community-associated staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection","volume":"9","author":"Randad","year":"2019","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"16663","DOI":"10.1038\/s41598-019-52982-0","article-title":"Development of a staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia and mixed infections","volume":"9","author":"Miller","year":"2019","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02451-21","article-title":"The novel oxazolidinone TBI-223 is effective in three preclinical mouse models of methicillin-resistant staphylococcus aureus infection","volume":"10","author":"Gordon","year":"2022","journal-title":"Microbiol Spectr"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.09.012","article-title":"IL-6R\/STAT3-signaling in keratinocytes rather than T cells induces psoriasis-like dermatitis in mice","volume":"142","author":"Ravipati","year":"2021","journal-title":"J Invest Dermatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501220","article-title":"Differential requirements of TCR signaling in homeostatic maintenance and function of dendritic epidermal T cells","volume":"195","author":"Zhang","year":"2015","journal-title":"J Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25027","article-title":"CCR2 contributes to host defense against staphylococcus aureus orthopedic implant-associated infections in mice","volume":"19","author":"Wang","year":"2021","journal-title":"J Orthop Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.012","article-title":"Interleukin-1 and related cytokines in the regulation of inflammation and immunity","volume":"50","author":"Mantovani","year":"2019","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.immuni.2018.11.015","article-title":"Cell-Type-Specific responses to interleukin-1 control microbial invasion and tumor-elicited inflammation in colorectal cancer","volume":"50","author":"Dmitrieva-Posocco","year":"2019","journal-title":"Immunity"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007800","article-title":"Staphylococcus aureus adhesion in endovascular infections is controlled by the ArlRS-MgrA signaling cascade","volume":"15","author":"Kwiecinski","year":"2019","journal-title":"PloS Pathog"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96481","article-title":"Clonally expanded \u03b3\u03b4 T cells protect against staphylococcus aureus skin reinfection","volume":"128","author":"Dillen","year":"2018","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.11.009","article-title":"Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses","volume":"30","author":"Ishigame","year":"2009","journal-title":"Immunity"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005226","article-title":"Memory Th1 cells are protective in invasive staphylococcus aureus infection","volume":"11","author":"Brown","year":"2015","journal-title":"PloS Pathog"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5207","article-title":"Critical role of signaling through IL-1 receptor for development of arthritis and sepsis during staphylococcus aureus infection","volume":"168","author":"Hultgren","year":"2002","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.08.009","article-title":"IL-1 receptor-associated kinase 1 mediates protection against staphylococcus aureus infection","volume":"6","author":"Verdrengh","year":"2004","journal-title":"Microbes Infect"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301237","article-title":"Influenza a exacerbates staphylococcus aureus pneumonia by attenuating IL-1\u03b2 production in mice","volume":"191","author":"Robinson","year":"2013","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601342","article-title":"Alarmins: feel the stress","volume":"198","author":"Rider","year":"2017","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol Rev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.4","article-title":"IL-1 pathways in inflammation and human diseases","volume":"6","author":"Gabay","year":"2010","journal-title":"Nat Rev Rheumatol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"14756","DOI":"10.1038\/srep14756","article-title":"IL-1\u03b1 is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity","volume":"5","author":"Cohen","year":"2015","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00596-16","article-title":"Interleukin-17A (IL-17A) and IL-17F are critical for antimicrobial peptide production and clearance of staphylococcus aureus nasal colonization","volume":"84","author":"Archer","year":"2016","journal-title":"Infect Immun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002194","article-title":"Influenza a inhibits Th17-mediated host defense against bacterial pneumonia in mice","volume":"186","author":"Kudva","year":"2011","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.3.619","article-title":"Group a streptococcal bacteremia: the role of tumor necrosis factor in shock and organ failure","volume":"173","author":"Stevens","year":"1996","journal-title":"J Infect Dis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/sj.cdd.4401189","article-title":"Tumor necrosis factor signaling","volume":"10","author":"Wajant","year":"2003","journal-title":"Cell Death Differ"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3930","article-title":"Clinical targeting of the TNF and TNFR superfamilies","volume":"12","author":"Croft","year":"2013","journal-title":"Nat Rev Drug Discovery"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01061-15","article-title":"Nonredundant roles of interleukin-17A (IL-17A) and IL-22 in murine host defense against cutaneous and hematogenous infection due to methicillin-resistant staphylococcus aureus","volume":"83","author":"Chan","year":"2015","journal-title":"Infect Immun"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003047","article-title":"Neutrophil-derived IL-1\u03b2 is sufficient for abscess formation in immunity against staphylococcus aureus in mice","volume":"8","author":"Cho","year":"2012","journal-title":"PloS Pathog"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00084-13","article-title":"Clearance of staphylococcus aureus nasal carriage is T cell dependent and mediated through interleukin-17A expression and neutrophil influx","volume":"81","author":"Archer","year":"2013","journal-title":"Infect Immun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.24","article-title":"Interleukin-22 regulates antimicrobial peptide expression and keratinocyte differentiation to control staphylococcus aureus colonization of the nasal mucosa","volume":"9","author":"Mulcahy","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.08.001","article-title":"Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity","volume":"31","author":"Sutton","year":"2009","journal-title":"Immunity"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.01.005","article-title":"Microbial colonization drives expansion of IL-1 receptor 1-expressing and IL-17-producing gamma\/delta T cells","volume":"7","author":"Duan","year":"2010","journal-title":"Cell Host Microbe"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812266115","article-title":"Blocking IL-1\u03b2 reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation","volume":"116","author":"Kaplanov","year":"2019","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B45","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.immuni.2017.10.016","article-title":"Targeting interleukin-1\u03b2 protects from aortic aneurysms induced by disrupted transforming growth factor \u03b2 signaling","volume":"47","author":"Da Ros","year":"2017","journal-title":"Immunity"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019574108","article-title":"Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface","volume":"108","author":"Ismail","year":"2011","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00452-4","article-title":"\u03b3\u03b4 T cells in tissue physiology and surveillance","volume":"21","author":"Ribot","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/j.immuni.2022.06.021","article-title":"Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a\/b to prevent skin dysbiosis and bacterial infection","volume":"55","author":"Dong","year":"2022","journal-title":"Immunity"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131645","article-title":"IL-1 receptor antagonist treatment aggravates staphylococcal septic arthritis and sepsis in mice","volume":"10","author":"Ali","year":"2015","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","first-page":"8369","DOI":"10.1038\/ncomms9369","article-title":"Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide","volume":"6","author":"Corriden","year":"2015","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701521","article-title":"Proximal","volume":"203","author":"Fiala","year":"2019","journal-title":"J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1171934\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T13:15:45Z","timestamp":1688735745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1171934\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,7]]},"references-count":51,"alternative-id":["10.3389\/fimmu.2023.1171934"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1171934","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,7]]},"article-number":"1171934"}}