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  • 1 Charité — University Medicine Berlin, Berlin, Germany
  • 2 Free University Berlin, Berlin, Germany

We have previously shown that Arcobacter butzleri induces intestinal, extra-intestinal, and systemic immune responses in perorally infected gnotobiotic IL-10−/− mice in a strain-dependent fashion. Here, we present a comprehensive survey of small and large intestinal expression profiles of inflammatory and regulatory mediators as well as of the matrix-degrading gelatinases MMP-2 and MMP-9 following murine A. butzleri infection. Gnotobiotic IL-10−/− mice were infected with A. butzleri strains CCUG 30485 or C1 of human and chicken origin, respectively. At day 6 following A. butzleri infection, mucin-2 mRNA, an integral part of the intestinal mucus layer, was downregulated in the colon, whereas TNF and IL-23p19 mRNA were upregulated in the ileum. Furthermore, IFN-γ, IL-17A, IL-1β, and IL-22 mRNA were upregulated in both colonic and ileal ex vivo biopsies at day 6 post strain CCUG 30485 infection. These changes were accompanied by downregulated colonic MMP-9 levels, whereas both MMP-2 and MMP-9 mRNA were upregulated in the ileum. In conclusion, these data indicate that A. butzleri infection induces changes in the expression of genes involved in pro-inflammatory and regulatory immune responses as well as in tissue degradation.

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  • 1.

    Ho HT , Lipman LJ, Gaastra W: Arcobacter, what is known and unknown about a potential foodborne zoonotic agent! Vet Microbiol 115(1–3), 113 (2006)

    • Search Google Scholar
    • Export Citation
  • 2.

    ICMSF ICoMSfF (2002): In: Microbiological Testing in Food Safety Management, 7, ed. Tompkin RB, Kluwer Academic/Plenum Publishers, New York, NY, p. 171

    • Search Google Scholar
    • Export Citation
  • 3.

    Collado L , Figueras MJ: Taxonomy, epidemiology, and clinical relevance of the genus Arcobacter. Clin Microbiol Rev 24(1), 174192 (2011)

    • Search Google Scholar
    • Export Citation
  • 4.

    Lappi V , Archer JR, Cebelinski E, Leano F, Besser JM, Klos RF, Medus C, Smith KE, Fitzgerald C, Davis JP: An outbreak of foodborne illness among attendees of a wedding reception in Wisconsin likely caused by Arcobacter butzleri. Foodborne Pathog Dis 10(3), 250255 (2013)

    • Search Google Scholar
    • Export Citation
  • 5.

    Bereswill S , Fischer A, Plickert R, Haag LM, Otto B, Kuhl AA, Dasti JI, Zautner AE, Munoz M, Loddenkemper C, Gross U, Gobel UB, Heimesaat MM: Novel murine infection models provide deep insights into the “menage a trois” of Campylobacter jejuni, microbiota and host innate immunity. PloS One 6(6), e20953 (2011)

    • Search Google Scholar
    • Export Citation
  • 6.

    Vandamme P , Pugina P, Benzi G, Van E tterijck R, Vlaes L, Kersters K, Butzler JP, Lior H, Lauwers S: Outbreak of recurrent abdominal cramps associated with Arcobacter butz leri in an Italian school. J Clin Microbiol 30(9), 23352337 (1992)

    • Search Google Scholar
    • Export Citation
  • 7.

    Karadas G , Sharbati S, Hanel I, Messelhausser U, Glocker E, Alter T, Gölz G: Presence of virulence genes, adhesion and invasion of Arcobacter butzleri. J Appl Microbiol 115(2), 583590 (2013)

    • Search Google Scholar
    • Export Citation
  • 8.

    Gölz G , Karadas G, Alutis ME, Fischer A, Kuhl AA, Breithaupt A, Gobel UB, Alter T, Bereswill S, Heimesaat MM: Arcobacter butzleri induce colonic, extra-intestinal and systemic inflammatory responses in gnotobiotic IL-10 deficient mice in a strain-dependent manner. PloS One 10(9), e0139402 (2015)

    • Search Google Scholar
    • Export Citation
  • 9.

    Heimesaat MM , Karadas G, Alutis M, Fischer A, Kuhl AA, Breithaupt A, Gobel UB, Alter T, Bereswill S, Gölz G: Survey of small intestinal and systemic immune responses following murine Arcobacter butzleri infection. Gut Pathog 7, 28 (2015)

    • Search Google Scholar
    • Export Citation
  • 10.

    Heimesaat MM , Bereswill S, Fischer A, Fuchs D, Struck D, Niebergall J, Jahn HK, Dunay IR, Moter A, Gescher DM, Schumann RR, Gobel UB, Liesenfeld O: Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii. J Immunol 177(12), 87858795 (2006)

    • Search Google Scholar
    • Export Citation
  • 11.

    Haag LM , Fischer A, Otto B, Plickert R, Kuhl AA, Gobel UB, Bereswill S, Heimesaat MM: Campylobacter jejuni induces acute enterocolitis in gnotobiotic IL-10-/- mice via Toll-like-receptor-2 and -4 signaling. PloS One 7(7), e40761 (2012)

    • Search Google Scholar
    • Export Citation
  • 12.

    Heimesaat MM , Lugert R, Fischer A, Alutis M, Kuhl AA, Zautner AE, Tareen AM, Gobel UB, Bereswill S: Impact of Campylobacter jejuni cj0268c knockout mutation on intestinal colonization, translocation, and induction of immunopathology in gnotobiotic IL-10 deficient mice. PloS One 9(2), e90148 (2014)

    • Search Google Scholar
    • Export Citation
  • 13.

    Gölz G , Karadas G, Fischer A, Gobel UB, Alter T, Bereswill S, Heimesaat MM: Toll-like receptor-4 is essential for Arcobacter butzleri-induced colonic and systemic immune responses in gnotobiotic IL-10-/- mice. Eur J Microbiol Immunol 5(4), 321332 (2015)

    • Search Google Scholar
    • Export Citation
  • 14.

    Heimesaat MM , Karadas G, Fischer A, Gobel UB, Alter T, Bereswill S, Gölz G: Toll-lLike receptor-4 dependent small intestinal immune responses following murine Arcobacter butzleri infection. Eur J Microbiol Immunol 5(4), 333342 (2015)

    • Search Google Scholar
    • Export Citation
  • 15.

    Munoz M , Heimesaat MM, Danker K, Struck D, Lohmann U, Plickert R, Bereswill S, Fischer A, Dunay IR, Wolk K, Loddenkemper C, Krell HW, Libert C, Lund LR, Frey O, Holscher C, Iwakura Y, Ghilardi N, Ouyang W, Kamradt T, Sabat R, Liesenfeld O: Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J Exp Med 206(13), 30473059 (2009)

    • Search Google Scholar
    • Export Citation
  • 16.

    McGuckin MA , Linden SK, Sutton P, Florin TH: Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9(4), 265278 (2011)

  • 17.

    Velcich A , Yang W, Heyer J, Fragale A, Nicholas C, Viani S, Kucherlapati R, Lipkin M, Yang K, Augenlicht L: Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295(5560), 17261729 (2002)

    • Search Google Scholar
    • Export Citation
  • 18.

    Buonocore S , Ahern PP, Uhlig HH, Ivanov, II, Littman DR, Maloy KJ, Powrie F: Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464(7293), 13711375 (2010)

    • Search Google Scholar
    • Export Citation
  • 19.

    Alutis ME , Grundmann U, Fischer A, Hagen U, Kuhl AA, Gobel UB, Bereswill S, Heimesaat MM: The role of gelatinases in Campylobacter jejuni infection of gnotobiotic mice. Eur J Microbiol Immunol 5(4), 256267 (2015)

    • Search Google Scholar
    • Export Citation
  • 20.

    Alutis ME , Grundmann U, Fischer A, Kuhl AA, Bereswill S, Heimesaat MM: Selective gelatinase inhibition reduces apoptosis and pro-inflammatory immune cell responses in Campylobacter jejuni-infected gnotobiotic IL-10 deficient mice. Eur J Microbiol Immunol 4(4), 213222 (2014)

    • Search Google Scholar
    • Export Citation
  • 21.

    Alutis ME , Grundmann U, Hagen U, Fischer A, Kuhl AA, Gobel UB, Bereswill S, Heimesaat MM: Matrix metalloproteinase- 2 mediates intestinal immunopathogenesis in Campylobacter jejuni-infected infant mice. Eur J Microbiol Immunol 5(3), 188198 (2015)

    • Search Google Scholar
    • Export Citation
  • 22.

    Birkedal-Hansen H , Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA: Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4(2), 197250 (1993)

    • Search Google Scholar
    • Export Citation
  • 23.

    Goetzl EJ , Banda MJ, Leppert D: Matrix metalloproteinases in immunity. J Immunol 156(1), 14 (1996)

  • 24.

    Strugala V , Allen A, Dettmar PW, Pearson JP: Colonic mucin: methods of measuring mucus thickness. P Nutr Soc 62(1), 237243 (2003)

  • 25.

    Hugdahl MB , Beery JT, Doyle MP: Chemotactic behavior of Campylobacter jejuni. Infect Immun 56(6), 15601566 (1988)

  • 26.

    Tu QV , McGuckin MA, Mendz GL: Campylobacter jejuni response to human mucin MUC2: modulation of colonization and pathogenicity determinants. J Med Microbiol 57(Pt 7), 795802 (2008)

    • Search Google Scholar
    • Export Citation
  • 27.

    Otto B , Haag LM, Fischer A, Plickert R, Kuhl AA, Gobel UB, Heimesaat MM, Bereswill S: Campylobacter jejuni induces extra-intestinal immune responses via Toll-likereceptor- 4 signaling in conventional IL-10 deficient mice with chronic colitis. Eur J Microbiol Immunol 2(3), 210219 (2012)

    • Search Google Scholar
    • Export Citation
  • 28.

    Petersson J , Schreiber O, Hansson GC, Gendler SJ, Velcich A, Lundberg JO, Roos S, Holm L, Phillipson M: Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 300(2), G327333 (2011)

    • Search Google Scholar
    • Export Citation
  • 29.

    Edwards LA , Nistala K, Mills DC, Stephenson HN, Zilbauer M, Wren BW, Dorrell N, Lindley KJ, Wedderburn LR, Bajaj-Elliott M: Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. PloS One 5(11), e15398 (2010)

    • Search Google Scholar
    • Export Citation
  • 30.

    Malik A , Sharma D, St C harles J, Dybas LA, Mansfield LS: Contrasting immune responses mediate Campylobacter jejuni-induced colitis and autoimmunity. Mucosal Immunol 7(4), 802817 (2014)

    • Search Google Scholar
    • Export Citation
  • 31.

    Zilbauer M , Dorrell N, Boughan PK, Harris A, Wren BW, Klein NJ, Bajaj-Elliott M: Intestinal innate immunity to Campylobacter jejuni results in induction of bactericidal human beta-defensins 2 and 3. Infect Immun 73(11), 72817289 (2005)

    • Search Google Scholar
    • Export Citation
  • 32.

    Ouyang W , Kolls JK, Zheng Y: The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28(4), 454467 (2008)

    • Search Google Scholar
    • Export Citation
  • 33.

    Zenewicz LA , Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA: Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29(6), 947957 (2008)

    • Search Google Scholar
    • Export Citation
  • 34.

    Zheng Y , Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, de Sauvage FJ, Ouyang W: Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14(3), 282289 (2008)

    • Search Google Scholar
    • Export Citation
  • 35.

    Munoz M , Eidenschenk C, Ota N, Wong K, Lohmann U, Kuhl AA, Wang X, Manzanillo P, Li Y, Rutz S, Zheng Y, Diehl L, Kayagaki N, van Lookeren-Campagne M, Liesenfeld O, Heimesaat M, Ouyang W: Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection. Immunity 42(2), 321331 (2015)

    • Search Google Scholar
    • Export Citation
  • 36.

    Salmela MT , MacDonald TT, Black D, Irvine B, Zhuma T, Saarialho-Kere U, Pender SL: Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisation. Gut 51(4), 540547 (2002)

    • Search Google Scholar
    • Export Citation
  • 37.

    Heimesaat MM , Dunay IR, Fuchs D, Trautmann D, Fischer A, Kuhl AA, Loddenkemper C, Siegmund B, Batra A, Beres will S, Liesenfeld O: The distinct roles of MMP-2 and MMP-9 in acute DSS colitis. Eur J Microbiol Immunol 1(4), 302310 (2011)

    • Search Google Scholar
    • Export Citation

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