{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:16:43Z","timestamp":1790338603122,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Although the abilities of the omentum to alleviate inflammation and prevent infection have been revealed over the past decades, the underlying mechanisms remain largely unelucidated. Here, we demonstrated that the mortality of mice exposed to cecal ligation and puncture (CLP) and omentectomy was remarkably increased compared to those treated with CLP alone. Moreover, the efficacy of the omentum was associated with an impairment in intraperitoneal bacterial clearance together with an increase in the expression of proinflammatory cytokines. Besides, in response to peritoneal infections, the size and quantity of the omental milky spots (MSs) were increased tremendously and they also support innate-like B1 cell responses and local IgM production in the peritoneal cavity. Furthermore, not only the migration but also the functional activities of neutrophils were diminished in the absence of the omentum. These data collectively show that the omentum contributes more to peritoneal immune responses during septic peritonitis than has heretofore been recognized. Thus, harnessing the function of MS-containing omentum to increase its protective effectiveness may exert important biological and therapeutic implications for the control of intra-abdominal infections.<\/jats:p>","DOI":"10.3389\/fimmu.2021.631609","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T04:56:05Z","timestamp":1616043365000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["The Essential Involvement of the Omentum in the Peritoneal Defensive Mechanisms During Intra-Abdominal Sepsis"],"prefix":"10.3389","volume":"12","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-nan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-ming","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-7922-9-22","article-title":"Current concept of abdominal sepsis: WSES position paper","volume":"9","author":"Sartelli","year":"2014","journal-title":"World J Emerg Surg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10828","article-title":"Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules","volume":"7","author":"Buscher","year":"2016","journal-title":"Nat Commun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/shk.0b013e318063e6ca","article-title":"The innate immune response to secondary peritonitis","volume":"28","author":"Till","year":"2007","journal-title":"Shock"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/shk.0000000000001311","article-title":"The Contribution of the Omentum to the Outcome From Sepsis: An Experimental Animal Study","volume":"52","author":"Wang","year":"2019","journal-title":"Shock"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ni1130","article-title":"Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells","volume":"15","author":"Zhang","year":"2014","journal-title":"Nat Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.03.014","article-title":"Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens","volume":"30","author":"Rangel-Moreno","year":"2009","journal-title":"Immunity"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.03.002","article-title":"Immunological Functions of the Omentum","volume":"38","author":"Meza-Perez","year":"2017","journal-title":"Trends Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature08636","article-title":"Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells","volume":"463","author":"Moro","year":"2010","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.4208","article-title":"Essential involvement of CX3CR1-mediated signals in the bactericidal host defense during septic peritonitis","author":"Ishida","year":"2008","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv562","article-title":"Toll-like Receptor 4 Signaling on Dendritic Cells Suppresses Polymorphonuclear Leukocyte CXCR2 Expression and Trafficking via Interleukin 10 During Intra-abdominal Sepsis","volume":"213","author":"Deng","year":"2016","journal-title":"J Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.4.508","article-title":"Induction of NOS in rat blood PMN in vivo and in vitro: modulation by tyrosine kinase and involvement in bactericidal activity","volume":"65","author":"Fierro","year":"1999","journal-title":"J Leukoc Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0185(199602)244:2<235::aid-ar11>3.0.co;2-q","article-title":"Omental milky spots in the local immune response in the peritoneal cavity of rats","volume":"244","author":"Van Vugt","year":"1996","journal-title":"Anat Rec"},{"key":"B13","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1093\/infdis\/jiaa441","article-title":"The autocrine regulation of Interleukin-3 on the activity of regulatory T cells and its effectiveness in the pathophysiology of sepsis","volume":"223","author":"Zhao","year":"2020","journal-title":"J Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1602056","article-title":"B-1a Cells Protect Mice from Sepsis: Critical Role of cAMP-response Element Binding Protein (CREB)","volume":"199","author":"Aziz","year":"2017","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0272OC","article-title":"Therapeutic Targeting of Apoptosis Inhibitor of Macrophage (AIM)\/CD5L in Sepsis","volume":"60","author":"Gao","year":"2018","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3215","article-title":"Inflammation-induced formation of fat-associated lymphoid clusters","volume":"16","author":"B\u00e9n\u00e9zech","year":"2015","journal-title":"Nat Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800713.","article-title":"GM-CSF Administration Improves Defects in Innate Immunity and Sepsis Survival in Obese Diabetic Mice","author":"Frydrych","year":"2018","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122244799","article-title":"A critical concentration of neutrophils is required for effective bacterial killing in suspension","volume":"99","author":"Li","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/00075198-200104000-00009","article-title":"Defense mechanisms of the peritoneal cavity","volume":"7","author":"Broche","year":"2001","journal-title":"Curr Opin Crit Care"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900409","article-title":"Lymphocytes in the peritoneum home to the omentum and are activated by resident dendritic cells","volume":"183","author":"Carlow","year":"2009","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131471","article-title":"Pleural innate response activator B cells protect against pneumonia via a GM-CSF-IgM axis","volume":"211","author":"Weber","year":"2014","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/bf02049895","article-title":"Let sleeping dogs lie: role of the omentum in the ileal pouch-anal anastomosis procedure","volume":"34","author":"Ambroze","year":"1991","journal-title":"Dis Colon Rectum"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-009-0855-1","article-title":"The Omentum: Anatomical, Metabolic, and Surgical Aspects[J]","volume":"13","author":"Collins","year":"2009","journal-title":"J Gastrointestinal Surg"},{"key":"B24","article-title":"The influence of omentectomy on bacterial clearance: an experimental study","volume":"15","author":"Uzunk\u00f6y","year":"2009","journal-title":"Ulus Travma Acil Cerrahi Derg"},{"key":"B25","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/nri2901","article-title":"The double life of a B-1 cell: self-reactivity selects for protective effector functions","volume":"11","author":"Baumgarth","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1177\/089686080502500111","article-title":"Omental milky spots and peritoneal dialysis\u2013review and personal experience","volume":"25","author":"Di Paolo","year":"2005","journal-title":"Perit Dial Int"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/SHK.0b013e3181818466","article-title":"The role of neutrophils in severe sepsis","author":"Alves-Filho","year":"2008","journal-title":"Shock"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.1999.00237.x","article-title":"TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii","volume":"21","author":"Liesenfeld","year":"1999","journal-title":"Parasite Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1590\/s0074-02762005000900038","article-title":"Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome","author":"Alves-Filho","year":"2005","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2174\/187153006777442404","article-title":"Neutrophil function in severe sepsis","volume":"6","author":"Alves-Filho","year":"2006","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"B31","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1186\/cc1853","article-title":"Science review: Cell membrane expression (connectivity) regulates neutrophil delivery, function and clearance","volume":"7","author":"Seely","year":"2003","journal-title":"Crit Care"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127542","article-title":"TLR9 signaling in fibroblastic reticular cells regulates peritoneal immunity","volume":"129","author":"Xu","year":"2019","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-015-8708-3","article-title":"The role of B-1 cells in inflammation","volume":"63","author":"Aziz","year":"2015","journal-title":"Immunol Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.08.002","article-title":"B-1 cells temper endotoxemic inflammatory responses","volume":"216","author":"Barbeiro","year":"2011","journal-title":"Immunobiology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nm1633","article-title":"Adaptive immune cells temper initial innate responses","volume":"13","author":"Kim","year":"2007","journal-title":"Nat Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062013","article-title":"Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells","volume":"204","author":"Zhang","year":"2007","journal-title":"J Exp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.631609\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T04:56:07Z","timestamp":1616043367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.631609\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2021.631609"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.631609","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"article-number":"631609"}}