{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:04:15Z","timestamp":1787501055117,"version":"build-2736575974"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-\u03b1 and IL-12, and increases IL-10 in macrophages. Because TNF-\u03b1 is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli\u2013induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-\u03b1, IL-1\u03b2, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli. Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture\u2013induced sepsis, rPPE18 reduced TNF-\u03b1, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis.<\/jats:p>","DOI":"10.4049\/jimmunol.1602065","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T12:03:16Z","timestamp":1524052996000},"page":"3587-3598","source":"Crossref","is-referenced-by-count":24,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis"],"prefix":"10.1093","volume":"200","author":[{"given":"Asma","family":"Ahmed","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics , Hyderabad - 500039, Telangana State,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Dolasia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics , Hyderabad - 500039, Telangana State,","place":["India"]},{"name":"Graduate Studies, Manipal Academy of Higher Education , Manipal - 576104, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangita","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics , Hyderabad - 500039, Telangana State,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"2025030610150561600_r1","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1378\/chest.127.3.942","article-title":"Incidence and impact of organ dysfunctions associated with sepsis","volume":"127","author":"Guidet","year":"2005","journal-title":"Chest"},{"key":"2025030610150561600_r2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/00024382-199504000-00001","article-title":"Interleukin-1 and interleukin-1 antagonism in sepsis, systemic inflammatory response syndrome, and septic shock","volume":"3","author":"Pruitt","year":"1995","journal-title":"Shock"},{"key":"2025030610150561600_r3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1378\/chest.99.1.169","article-title":"Endotoxemia in human septic shock","volume":"99","author":"Danner","year":"1991","journal-title":"Chest"},{"key":"2025030610150561600_r4","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1001\/jama.1992.03490240060037","article-title":"Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome)","volume":"268","author":"Bone","year":"1992","journal-title":"JAMA"},{"key":"2025030610150561600_r5","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1378\/chest.101.6.1481","article-title":"The ACCP-SCCM consensus conference on sepsis and organ failure","volume":"101","author":"Bone","year":"1992","journal-title":"Chest"},{"key":"2025030610150561600_r6","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat. 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