{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:04:50Z","timestamp":1790391890025,"version":"4.1.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":[[2011,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nucleotide-binding oligomerization domain 2 (Nod2) mutations including L1007fsinsC are associated with the development of Crohn\u2019s disease (CD). These CD-associated Nod2 mutations are common in healthy white populations, suggesting that they may confer some protective function, but experimental evidence is lacking. Using a mouse strain that expresses Nod22939iCstop, the equivalent of the L1007fsinsC mutation, we found that macrophages homozygous for Nod22939iCstop are impaired in the recognition of muramyl dipeptide and Enterococcus faecalis, a commensal bacterium that is a common cause of sepsis-associated lethality in humans. Notably, Nod2 deficiency and homozygocity for Nod22939iCstop were associated with reduced production of TNF-\u03b1 and IL-6 and lethality after systemic infection with E. faecalis despite normal bacteria loads. Consistently, inhibition of TNF-\u03b1 signaling protected wild-type mice from E. faecalis-induced lethality. These results suggest that the same Nod2 mutation can increase the susceptibility to CD, but also protect the host from systemic infection by a common enteric bacterium.<\/jats:p>","DOI":"10.4049\/jimmunol.1001854","type":"journal-article","created":{"date-parts":[[2011,8,22]],"date-time":"2011-08-22T13:07:53Z","timestamp":1314018473000},"page":"2849-2852","source":"Crossref","is-referenced-by-count":56,"title":["Cutting Edge: Crohn\u2019s Disease-Associated Nod2 Mutation Limits Production of Proinflammatory Cytokines To Protect the Host from\n                    <i>Enterococcus faecalis<\/i>\n                    -Induced Lethality"],"prefix":"10.1093","volume":"187","author":[{"given":"Yun-Gi","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Warner","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,9,15]]},"reference":[{"key":"2025032410334409500_r1","doi-asserted-by":"crossref","first-page":"8869","DOI":"10.1074\/jbc.C200651200","article-title":"Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection","volume":"278","author":"Girardin","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2025032410334409500_r2","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1074\/jbc.C200673200","article-title":"Host recognition of bacterial muramyl dipeptide mediated through NOD2: implications for Crohn\u2019s disease","volume":"278","author":"Inohara","year":"2003","journal-title":"J. Biol. 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