Markus M Heimesaat, Ursula Grundmann, Marie E Alutis, André Fischer, Stefan Bereswill
{"title":"缺乏核苷酸寡聚结构域-2的继发性非生物IL-10-/-小鼠空肠弯曲杆菌感染后的小肠促炎免疫反应","authors":"Markus M Heimesaat, Ursula Grundmann, Marie E Alutis, André Fischer, Stefan Bereswill","doi":"10.1556/1886.2017.00005","DOIUrl":null,"url":null,"abstract":"<p><p>Host immune responses are crucial for combating enteropathogenic infections including <i>Campylobacter jejuni</i>. Within 1 week following peroral <i>C. jejuni</i> infection, secondary abiotic IL-10<sup>-/-</sup> mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, <i>C. jejuni</i> stably colonized the gastrointestinal tract of both IL-10<sup>-/-</sup> mice lacking Nod2 (Nod2<sup>-/-</sup> IL-10<sup>-/-</sup>) and IL-10<sup>-/-</sup> controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of <i>C. jejuni</i>-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in <i>C. jejuni</i>-infected Nod2<sup>-/-</sup> IL-10<sup>-/-</sup> as compared to IL-10<sup>-/-</sup> counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal <i>ex vivo</i> biopsies derived from <i>C. jejuni</i>-infected mice of either genotype. In conclusion, <i>C. jejuni</i>-induced pro-inflammatory immune responses affected the small intestines of both Nod2<sup>-/-</sup> IL-10<sup>-/-</sup> and IL-10<sup>-/-</sup> mice, whereas ileal T lymphocyte numbers were even higher in the former.</p>","PeriodicalId":11929,"journal":{"name":"European Journal of Microbiology & Immunology","volume":"7 2","pages":"138-145"},"PeriodicalIF":0.0000,"publicationDate":"2017-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1556/1886.2017.00005","citationCount":"8","resultStr":"{\"title\":\"Small Intestinal Pro-Inflammatory Immune Responses Following <i>Campylobacter Jejuni</i> Infection of Secondary Abiotic IL-10<sup>-/-</sup> Mice Lacking Nucleotide-Oligomerization-Domain-2.\",\"authors\":\"Markus M Heimesaat, Ursula Grundmann, Marie E Alutis, André Fischer, Stefan Bereswill\",\"doi\":\"10.1556/1886.2017.00005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Host immune responses are crucial for combating enteropathogenic infections including <i>Campylobacter jejuni</i>. Within 1 week following peroral <i>C. jejuni</i> infection, secondary abiotic IL-10<sup>-/-</sup> mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, <i>C. jejuni</i> stably colonized the gastrointestinal tract of both IL-10<sup>-/-</sup> mice lacking Nod2 (Nod2<sup>-/-</sup> IL-10<sup>-/-</sup>) and IL-10<sup>-/-</sup> controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of <i>C. jejuni</i>-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in <i>C. jejuni</i>-infected Nod2<sup>-/-</sup> IL-10<sup>-/-</sup> as compared to IL-10<sup>-/-</sup> counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal <i>ex vivo</i> biopsies derived from <i>C. jejuni</i>-infected mice of either genotype. In conclusion, <i>C. jejuni</i>-induced pro-inflammatory immune responses affected the small intestines of both Nod2<sup>-/-</sup> IL-10<sup>-/-</sup> and IL-10<sup>-/-</sup> mice, whereas ileal T lymphocyte numbers were even higher in the former.</p>\",\"PeriodicalId\":11929,\"journal\":{\"name\":\"European Journal of Microbiology & Immunology\",\"volume\":\"7 2\",\"pages\":\"138-145\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1556/1886.2017.00005\",\"citationCount\":\"8\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Microbiology & Immunology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1556/1886.2017.00005\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/6/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Microbiology & Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1556/1886.2017.00005","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/6/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
Small Intestinal Pro-Inflammatory Immune Responses Following Campylobacter Jejuni Infection of Secondary Abiotic IL-10-/- Mice Lacking Nucleotide-Oligomerization-Domain-2.
Host immune responses are crucial for combating enteropathogenic infections including Campylobacter jejuni. Within 1 week following peroral C. jejuni infection, secondary abiotic IL-10-/- mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, C. jejuni stably colonized the gastrointestinal tract of both IL-10-/- mice lacking Nod2 (Nod2-/- IL-10-/-) and IL-10-/- controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of C. jejuni-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in C. jejuni-infected Nod2-/- IL-10-/- as compared to IL-10-/- counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal ex vivo biopsies derived from C. jejuni-infected mice of either genotype. In conclusion, C. jejuni-induced pro-inflammatory immune responses affected the small intestines of both Nod2-/- IL-10-/- and IL-10-/- mice, whereas ileal T lymphocyte numbers were even higher in the former.