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The infected mice displayed a significant up\u2010regulation in the expression of chemokines (<jats:italic>Cxcl1<\/jats:italic>,<jats:italic> Cxcl2<\/jats:italic> and <jats:italic>Ccl2<\/jats:italic>), numerous pro\u2010inflammatory cytokines (<jats:italic>Ifng<\/jats:italic>,<jats:italic> Il1b<\/jats:italic>,<jats:italic> Il6<\/jats:italic>, and <jats:italic>Il17f<\/jats:italic>), as well as <jats:italic>Il22<\/jats:italic> and a number of anti\u2010microbial peptides (<jats:italic>Defa1<\/jats:italic>,<jats:italic> Defa28<\/jats:italic>,<jats:italic> Defb1, Slpi<\/jats:italic> and <jats:italic>Reg3g<\/jats:italic>) at the site(s) of infection. This was accompanied by a significant influx of neutrophils, dendritic cells, cells of the monocyte\/macrophage lineage and all major subsets of lymphocytes to these site(s). However, CD4 T cells of the untreated and <jats:italic><jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>.\u00a0difficile<\/jats:italic>\u2010infected mice expressed similar levels of CD69 and CD25. Neither tissue had up\u2010regulated levels of <jats:italic>Tbx21<\/jats:italic>,<jats:italic> Gata3<\/jats:italic> or <jats:italic>Rorc<\/jats:italic>. The caeca and colons of the infected mice showed a significant increase in eukaryotic initiation factor 2\u03b1 (eIF2\u03b1) phosphorylation, but neither the splicing of <jats:italic>Xbp1<\/jats:italic> nor the up\u2010regulation of endoplasmic reticulum chaperones, casting doubt on the full\u2010fledged induction of the unfolded protein response by <jats:italic><jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>.\u00a0difficile<\/jats:italic>. They also displayed significantly higher phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), an indication of pro\u2010survival signalling. These data underscore the local, innate, pro\u2010inflammatory nature of the response to <jats:italic><jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>.\u00a0difficile<\/jats:italic> and highlight eIF2\u03b1 phosphorylation and the interleukin\u201022\u2013pSTAT3\u2013RegIII\u03b3 axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal epithelium.<\/jats:p>","DOI":"10.1111\/imm.12122","type":"journal-article","created":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T15:32:41Z","timestamp":1368459161000},"page":"111-122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Acute infection of mice with <i><scp>C<\/scp>lostridium difficile<\/i> leads to eIF2\u03b1 phosphorylation and pro\u2010survival signalling as part of the mucosal inflammatory response"],"prefix":"10.1111","volume":"140","author":[{"given":"Amir A.","family":"Sadighi Akha","sequence":"first","affiliation":[{"name":"Divisions of Pulmonary and Critical Care Medicine Department of Internal Medicine University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey M.","family":"Theriot","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department of Internal Medicine University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Erb\u2010Downward","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care Medicine Department of Internal Medicine University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"Falkowski","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care Medicine Department of Internal Medicine University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Tyra","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Carver College of Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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