Acute infection of mice with Clostridium difficile leads to eIF2α phosphorylation and pro-survival signalling as part of the mucosal inflammatory response

Immunology

Volumn 140, Issue 1, 2013, Pages 111-122

  Sadighi Akha, Amir A ^a,c   Theriot, Casey M ^a   Erb Downward, John R ^a   Mcdermott, Andrew J ^a   Falkowski, Nicole R ^a   Tyra, Heather M ^b   Rutkowski, D Thomas ^b   Young, Vincent B ^a   Huffnagle, Gary B ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c MAYO CLINIC   (United States)

Author keywords

Clostridium difficile; EIF2 ; Interleukin 22; PSTAT3; RegIII

Indexed keywords

CD69 ANTIGEN; CHAPERONE; CXCL1 CHEMOKINE; CXCL2 CHEMOKINE; GAMMA INTERFERON; INITIATION FACTOR 2ALPHA; INTERLEUKIN 1; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 22; INTERLEUKIN 6; INTERLEUKIN 7; MONOCYTE CHEMOTACTIC PROTEIN 1; POLYPEPTIDE ANTIBIOTIC AGENT; PROTEIN DEFA1; PROTEIN DEFA28; PROTEIN DEFB1; PROTEIN KINASE B; PROTEIN REG3G; PROTEIN SLPI; RETINOID RELATED ORPHAN RECEPTOR GAMMA; STAT3 PROTEIN; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR T BET; UNCLASSIFIED DRUG; X BOX BINDING PROTEIN 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; CD4+ T LYMPHOCYTE; CECUM; CELL LINEAGE; CLOSTRIDIUM DIFFICILE INFECTION; COLON; CONTROLLED STUDY; DENDRITIC CELL; ENDOPLASMIC RETICULUM; EXPERIMENTAL MODEL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; IMMUNE RESPONSE; INFLAMMATION; INNATE IMMUNITY; INTESTINE EPITHELIUM; LYMPHOCYTE SUBPOPULATION; MACROPHAGE; MALE; MONOCYTE; MOUSE; MUCOSAL IMMUNITY; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RNA SPLICING; SIGNAL TRANSDUCTION; SURVIVAL; UNFOLDED PROTEIN RESPONSE; UPREGULATION;

CLOSTRIDIUM DIFFICILE; EIF2Α; INTERLEUKIN-22; PSTAT3; REGIIIΓ;

ACUTE DISEASE; ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; CHEMOKINES; CLOSTRIDIUM DIFFICILE; CYTOKINES; ENTEROCOLITIS, PSEUDOMEMBRANOUS; EUKARYOTIC INITIATION FACTOR-2; IMMUNITY, INNATE; IMMUNITY, MUCOSAL; INFLAMMATION MEDIATORS; INTERLEUKINS; INTESTINAL MUCOSA; MALE; MICE; MICE, INBRED C57BL; PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSCRIPTOME; UNFOLDED PROTEIN RESPONSE;

EID: 84883225366     PISSN: 00192805     EISSN: 13652567     Source Type: Journal    
DOI: 10.1111/imm.12122     Document Type: Article

References (75)

1. Hall I, O'Toole E. Intestinal flora in newborn infants with description of a new pathogenic anaerobe. Am J Dis Child 1935; 49:390-402.
2. Kelly CP, LaMont JT. Clostridium difficile infection. Annu Rev Med 1998; 49:375-90.
3. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009; 7:526-36.
4. Just I, Selzer J, von Eichel-Streiber C, Aktories K. The low molecular mass GTP-binding protein Rho is affected by toxin A from Clostridium difficile. J Clin Invest 1995; 95:1026-31.
5. Just I, Selzer J, Wilm M, von Eichel-Streiber C, Mann M, Aktories K. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 1995; 375:500-3.
6. Hecht G, Pothoulakis C, LaMont JT, Madara JL. Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers. J Clin Invest 1988; 82:1516-24.
7. Hecht G, Koutsouris A, Pothoulakis C, LaMont JT, Madara JL. Clostridium difficile toxin B disrupts the barrier function of T84 monolayers. Gastroenterology 1992; 102:416-23.
8. Pothoulakis C, Lamont JT. Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins. Am J Physiol Gastrointest Liver Physiol 2001; 280:G178-83.
9. Best EL, Freeman J, Wilcox MH. Models for the study of Clostridium difficile infection. Gut Microbes 2012; 3:145-67.
10. Lawley TD, Clare S, Walker AW et al. Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect Immun 2009; 77:3661-9.
11. Ryan A, Lynch M, Smith SM et al. A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. PLoS Pathog 2011; 7:e1002076.
12. Jarchum I, Liu M, Lipuma L, Pamer EG. Toll-like receptor 5 stimulation protects mice from acute Clostridium difficile colitis. Infect Immun 2011; 79:1498-503.
13. Jarchum I, Liu M, Shi C, Equinda M, Pamer EG. Critical role for MyD88-mediated neutrophil recruitment during C. difficile colitis. Infect Immun 2012; 80:2989-96.
14. Hasegawa M, Yamazaki T, Kamada N, Tawaratsumida K, Kim YG, Nunez G, Inohara N. Nucleotide-binding oligomerization domain 1 mediates recognition of Clostridium difficile and induces neutrophil recruitment and protection against the pathogen. J Immunol 2011; 186:4872-80.
15. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature 2008; 454:455-62.
16. Martinon F, Glimcher LH. Regulation of innate immunity by signaling pathways emerging from the endoplasmic reticulum. Curr Opin Immunol 2011; 23:35-40.
17. Kaser A, Lee AH, Franke A et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 2008; 134:743-56.
18. Brandl K, Rutschmann S, Li X, Du X, Xiao N, Schnabl B, Brenner DA, Beutler B. Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response. Proc Natl Acad Sci USA 2009; 106:3300-5.
19. Cao SS, Song B, Kaufman RJ. PKR protects colonic epithelium against colitis through the unfolded protein response and prosurvival signaling. Inflamm Bowel Dis 2012; 18: 1735-42.
20. Schroder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem 2005; 74:739-89.
21. Lin JH, Walter P, Yen TS. Endoplasmic reticulum stress in disease pathogenesis. Annu Rev Pathol 2008; 3:399-425.
22. Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell 2000; 5:897-904.
23. Novoa I, Zhang Y, Zeng H, Jungreis R, Harding HP, Ron D. Stress-induced gene expression requires programmed recovery from translational repression. EMBO J 2003; 22:1180-7.
24. Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α. J Cell Biol 2001; 153:1011-22.
25. Boyce M, Bryant KF, Jousse C et al. A selective inhibitor of eIF2α dephosphorylation protects cells from ER stress. Science 2005; 307:935-9.
26. Sidrauski C, Walter P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell 1997; 90:1031-9.
27. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001; 107:881-91.
28. Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 2003; 23:7448-59.
29. Oda Y, Okada T, Yoshida H, Kaufman RJ, Nagata K, Mori K. Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J Cell Biol 2006; 172:383-93.
30. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 2000; 6:1355-64.
31. Wu J, Rutkowski DT, Dubois M et al. ATF6α optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell 2007; 13:351-64.
32. Yamamoto K, Sato T, Matsui T, Sato M, Okada T, Yoshida H, Harada A, Mori K. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6α and XBP1. Dev Cell 2007; 13:365-76.
33. Chen X, Katchar K, Goldsmith JD, Nanthakumar N, Cheknis A, Gerding DN, Kelly CP. A mouse model of Clostridium difficile-associated disease. Gastroenterology 2008; 135:1984-92.
34. Reeves AE, Theriot CM, Bergin IL, Huffnagle GB, Schloss PD, Young VB. The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile infection. Gut Microbes 2011; 2:145-58.
35. Theriot CM, Koumpouras CC, Carlson PE, Bergin II, Aronoff DM, Young VB. Cefoperazone-treated mice as an experimental platform to assess differential virulence of Clostridium difficile strains. Gut Microbes 2011; 2:326-34.
36. Reeves AE, Koenigsknecht MJ, Bergin IL, Young VB. Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect Immun 2012; 80:3786-94.
37. Weigmann B, Tubbe I, Seidel D, Nicolaev A, Becker C, Neurath MF. Isolation and subsequent analysis of murine lamina propria mononuclear cells from colonic tissue. Nat Protoc 2007; 2:2307-11.
38. Hunt SV. Preparation of lymphocytes and accessory cells. In: Klaus GGB, ed. Lymphocytes: A Practical Approach. Oxford: IRL Press, 1987: 1-34.
39. Sadighi Akha AA, Harper JM, Salmon AB, Schroeder BA, Tyra HM, Rutkowski DT., Miller RA. Heightened induction of proapoptotic signals in response to endoplasmic reticulum stress in primary fibroblasts from a mouse model of longevity. J Biol Chem 2011; 286:30344-30351.
40. Rutkowski DT, Arnold SM, Miller CN et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol 2006; 4:e374.
41. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3:RESEARCH0034.
42. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001; 98:5116-21.
43. Eash KJ, Greenbaum AM, Gopalan PK, Link DC. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest 2010; 120:2423-31.
44. Burdon PC, Martin C, Rankin SM. The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner. Blood 2005; 105:2543-8.
45. Struyf S, Van Collie E, Paemen L, Put W, Lenaerts JP, Proost P, Opdenakker G, Van Damme J. Synergistic induction of MCP-1 and -2 by IL-1β and interferons in fibroblasts and epithelial cells. J Leukoc Biol 1998; 63:364-72.
46. Lundahl J, Jacobson SH, Paulsson JM. IL-8 from local subcutaneous wounds regulates CD11b activation. Scand J Immunol 2012; 75:419-25.
47. Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 2009; 27:669-92.
48. Hirota SA, Fines K, Ng J et al. Hypoxia-inducible factor signaling provides protection in Clostridium difficile-induced intestinal injury. Gastroenterology 2010; 139(259-269):e253.
49. Castagliuolo I, Keates AC, Wang CC et al. Clostridium difficile toxin A stimulates macrophage-inflammatory protein-2 production in rat intestinal epithelial cells. J Immunol 1998; 160:6039-45.
50. Kim JM, Kim JS, Jun HC, Oh YK, Song IS, Kim CY. Differential expression and polarized secretion of CXC and CC chemokines by human intestinal epithelial cancer cell lines in response to Clostridium difficile toxin A. Microbiol Immunol 2002; 46:333-42.
51. Iyoda M, Shibata T, Kawaguchi M, Hizawa N, Yamaoka T, Kokubu F, Akizawa T. IL-17A and IL-17F stimulate chemokines via MAPK pathways (ERK1/2 and p38 but not JNK) in mouse cultured mesangial cells: synergy with TNF-α and IL-1β. Am J Physiol Renal Physiol 2010; 298:F779-87.
52. Hurst SD, Muchamuel T, Gorman DM et al. New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J Immunol 2002; 169:443-53.
53. Castellanos MC, Lopez-Giral S, Lopez-Cabrera M, de Landazuri MO. Multiple cis-acting elements regulate the expression of the early T cell activation antigen CD69. Eur J Immunol 2002; 32:3108-17.
54. John S, Reeves RB, Lin JX, Child R, Leiden JM, Thompson CB, Leonard WJ. Regulation of cell-type-specific interleukin-2 receptor α-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-κB family proteins. Mol Cell Biol 1995; 15:1786-96.
55. Sadighi Akha AA, Berger SB, Miller RA. Enhancement of CD8 T-cell function through modifying surface glycoproteins in young and old mice. Immunology 2006; 119:187-94.
56. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011; 29:71-109.
57. Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol 2011; 12:383-90.
58. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004; 21:241-54.
59. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006; 203:2271-9.
60. Zheng Y, Valdez PA, Danilenko DM et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 2008; 14:282-9.
61. Vaishnava S, Yamamoto M, Severson KM et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 2011; 334:255-8.
62. Ng J, Hirota SA, Gross O et al. Clostridium difficile toxin-induced inflammation and intestinal injury are mediated by the inflammasome. Gastroenterology 2010; 139:542-52. 552 e541-543.
63. Castagliuolo I, Kelly CP, Qiu BS, Nikulasson ST, LaMont JT, Pothoulakis C. IL-11 inhibits Clostridium difficile toxin A enterotoxicity in rat ileum. Am J Physiol 1997; 273:G333-41.
64. Ishida Y, Maegawa T, Kondo T, Kimura A, Iwakura Y, Nakamura S, Mukaida N. Essential involvement of IFN-γ in Clostridium difficile toxin A-induced enteritis. J Immunol 2004; 172:3018-25.
65. Morteau O, Castagliuolo I, Mykoniatis A et al. Genetic deficiency in the chemokine receptor CCR1 protects against acute Clostridium difficile toxin A enteritis in mice. Gastroenterology 2002; 122:725-33.
66. Rutkowski DT, Hegde RS. Regulation of basal cellular physiology by the homeostatic unfolded protein response. J Cell Biol 2010; 189:783-94.
67. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012; 13:89-102.
68. Garcia MA, Meurs EF, Esteban M. The dsRNA protein kinase PKR: virus and cell control. Biochimie 2007; 89:799-811.
69. Koch S, Nava P, Addis C, Kim W, Denning TL, Li L, Parkos CA, Nusrat A. The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair. Gastroenterology 2011; 141:259-68, 268 e251-258.
70. Sautin YY, Crawford JM, Svetlov SI. Enhancement of survival by LPA via Erk1/Erk2 and PI 3-kinase/Akt pathways in a murine hepatocyte cell line. Am J Physiol Cell Physiol 2001; 281:C2010-9.
71. Pickert G, Neufert C, Leppkes M et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009; 206:1465-72.
72. Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J Biol Chem 2002; 277:33676-82.
73. Dumoutier L, de Meester C, Tavernier J, Renauld JC. New activation modus of STAT3: a tyrosine-less region of the interleukin-22 receptor recruits STAT3 by interacting with its coiled-coil domain. J Biol Chem 2009; 284:26377-84.
74. Murray PJ. The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription. Proc Natl Acad Sci USA 2005; 102:8686-91.
75. Moreno JA, Radford H, Peretti D et al. Sustained translational repression by eIF2α-P mediates prion neurodegeneration. Nature 2012; 485:507-11.