Dendritic cell immunoreceptor 1 alters neutrophil responses in the development of experimental colitis

BMC Immunology

Kayo Inaba¹  Kazuhiko Takahara¹  Yoichiro Iwakura³  Toshifumi Ishiguro²  Marie Komori²  Sumika Tokieda² 

[1] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan;Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501, Japan;Present addresses: Research Institute for Biomedical Sciences, Tokyo University of Science, Yamasaki 2641, Noda, Chiba 278-0022, Japan

关键词: Neutrophil;    Myeloperoxidase;    DSS colitis;    DCIR;    C-type lectin receptor;   

Others  :  1233006
DOI  :  10.1186/s12865-015-0129-5

 received in 2015-07-25, accepted in 2015-10-20,  发布年份 2015

【 摘 要 】

Background

Ulcerative colitis, an inflammatory bowel disease, is associated with the massive infiltration of neutrophils. Although the initial infiltration of neutrophils is beneficial for killing bacteria, it is presumed that persistent infiltration causes tissue damage by releasing antibacterial products as well as inflammatory cytokines. A murine C-type lectin receptor, dendritic cell immunoreceptor 1 (Dcir1), is expressed on CD11b ⁺myeloid cells, such as macrophages, dendritic cells and neutrophils. It was reported that Dcir1 is required to maintain homeostasis of the immune system to prevent autoimmunity, but it is also involved in the development of infectious disease resulting in the enhanced severity of cerebral malaria. However, the role of Dcir1 in intestinal immune responses during colitis remains unclear. In this study, we investigated the role of Dcir1 in intestinal inflammation using an experimental colitis model induced with dextran sodium sulfate (DSS).

Results

In contrast to wild type (WT) mice, Dcir1 ^−/− mice exhibited mild body weight loss during the course of DSS colitis accompanied by reduced colonic inflammation. Dcir1 deficiency caused a reduced accumulation of neutrophils in the inflamed colon on day 5 of DSS colitis compared with WT mice. Consistently, the production of a neutrophil-attracting chemokine, MIP-2, was also decreased in the Dcir1 ^−/− colon compared with the WT colon on day 5. There were fewer myeloperoxidase-positive neutrophils in the inflamed colon of Dcir1 ^−/− mice than in that of WT mice. Moreover, bone marrow neutrophils from Dcir1 ^−/− mice produced less reactive oxygen species (ROS) by lipopolysaccharide stimulation than those from WT mice. This suggests that Dcir1 deficiency decreases the accumulation of tissue destructive neutrophils during DSS colitis.

Conclusion

Dcir1 enhances the pathogenesis of DSS colitis by altering neutrophil recruitment and their functions.

【 授权许可】

   
2015 Tokieda et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

【 参考文献 】

• [1]Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006; 12 Suppl 1:S3-9.
• [2]Neuman MG. Immune dysfunction in inflammatory bowel disease. Transl Res. 2007; 149:173-86.
• [3]Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010; 28:573-621.
• [4]Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011; 474:298-306.
• [5]Cho JH, Brant SR. Recent insights into the genetics of inflammatory bowel disease. Gastroenterology. 2011; 140:1704-12.
• [6]Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology. 2011; 140:1729-37.
• [7]Fournier BM, Parkos CA. The role of neutrophils during intestinal inflammation. Mucosal Immunol. 2012; 5:354-66.
• [8]Hampton MB, Kettle AJ, Winterbourn CC. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood. 1998; 92:3007-17.
• [9]Elliott SN, Wallace JL. Neutrophil-mediated gastrointestinal injury. Can J Gastroenterol. 1998; 12:559-68.
• [10]Hazen SL, Hsu FF, Mueller DM, Crowley JR, Heinecke JW. Human neutrophils employ chlorine gas as an oxidant during phagocytosis. J Clin Invest. 1996; 98:1283-9.
• [11]Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010; 140:805-20.
• [12]Walsh D, McCarthy J, O'Driscoll C, Melgar S. Pattern recognition receptors--molecular orchestrators of inflammation in inflammatory bowel disease. Cytokine Growth Factor Rev. 2013; 24:91-104.
• [13]Bates EE, Fournier N, Garcia E, Valladeau J, Durand I, Pin JJ et al.. APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif. J Immunol. 1999; 163:1973-83.
• [14]Sancho D, Reis e Sousa C. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol. 2012; 30:491-529.
• [15]Miyake Y, Ishikawa E, Ishikawa T, Yamasaki S. Self and nonself recognition through C-type lectin receptor. Mincle Self Nonself. 2010; 1:310-3.
• [16]Lambert AA, Gilbert C, Richard M, Beaulieu AD, Tremblay MJ. The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways. Blood. 2008; 112:1299-307.
• [17]Bloem K, Vuist IM, van den Berk M, Klaver EJ, van Die I, Knippels LM et al.. DCIR interacts with ligands from both endogenous and pathogenic origin. Immunol Lett. 2013; 158:33-41.
• [18]Kaden SA, Kurig S, Vasters K, Hofmann K, Zaenker KS, Schmitz J et al.. Enhanced dendritic cell-induced immune responses mediated by the novel C-type lectin receptor mDCAR1. J Immunol. 2009; 183:5069-78.
• [19]Kanazawa N, Okazaki T, Nishimura H, Tashiro K, Inaba K, Miyachi Y. DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine-based inhibitory motif. J Invest Dermatol. 2002; 118:261-6.
• [20]Fujikado N, Saijo S, Yonezawa T, Shimamori K, Ishii A, Sugai S et al.. Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. Nat Med. 2008; 14:176-80.
• [21]Maglinao M, Klopfleisch R, Seeberger PH, Lepenies B. The C-type lectin receptor DCIR is crucial for the development of experimental cerebral malaria. J Immunol. 2013; 191:2551-9.
• [22]Mitsuyama K, Toyonaga A, Sasaki E, Watanabe K, Tateishi H, Nishiyama T et al.. IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn’s disease. Clin Exp Immunol. 1994; 96:432-6.
• [23]Qualls JE, Kaplan AM, van Rooijen N, Cohen DA. Suppression of experimental colitis by intestinal mononuclear phagocytes. J Leukoc Biol. 2006; 80:802-15.
• [24]Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, Friedlander G et al.. Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity. 2012; 37:1076-90.
• [25]Kojouharoff G, Hans W, Obermeier F, Mannel DN, Andus T, Scholmerich J et al.. Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin Exp Immunol. 1997; 107:353-8.
• [26]Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y et al.. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011; 331:337-41.
• [27]Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990; 98:694-702.
• [28]Perse M, Cerar A. Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol. 2012; doi:10.1155/2012/718617.
• [29]Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E et al.. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998; 66:5224-31.
• [30]Clarke CJ, Stokes CR. The intestinal and serum humoral immune response of mice to orally administered antigens in liposomes: II. The response to liposome-entrapped bacterial proteins. Vet Immunol Immunopathol. 1992; 32:139-48.
• [31]Ohtsuka Y, Sanderson IR. Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial cell chemokine expression in mice. Pediatr Res. 2003; 53:143-7.
• [32]Zahn A, Giese T, Karner M, Braun A, Hinz U, Stremmel W et al.. Transcript levels of different cytokines and chemokines correlate with clinical and endoscopic activity in ulcerative colitis. BMC Gastroenterol. 2009; 9:13. BioMed Central Full Text
• [33]Podolin PL, Bolognese BJ, Foley JJ, Schmidt DB, Buckley PT, Widdowson KL et al.. A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol. 2002; 169:6435-44.
• [34]Ajuebor MN, Zagorski J, Kunkel SL, Strieter RM, Hogaboam CM. Contrasting roles for CXCR2 during experimental colitis. Exp Mol Pathol. 2004; 76:1-8.
• [35]Buanne P, Di Carlo E, Caputi L, Brandolini L, Mosca M, Cattani F et al.. Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice. J Leukoc Biol. 2007; 82:1239-46.
• [36]Farooq SM, Stillie R, Svensson M, Svanborg C, Strieter RM, Stadnyk AW. Therapeutic effect of blocking CXCR2 on neutrophil recruitment and dextran sodium sulfate-induced colitis. J Pharmacol Exp Ther. 2009; 329:123-9.
• [37]Williams EJ, Haque S, Banks C, Johnson P, Sarsfield P, Sheron N. Distribution of the interleukin-8 receptors, CXCR1 and CXCR2, in inflamed gut tissue. J Pathol. 2000; 192:533-9.
• [38]McKenzie SJ, Baker MS, Buffinton GD, Doe WF. Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. J Clin Invest. 1996; 98:136-41.
• [39]Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. 1998; 115:182-205.
• [40]Campieri M, Gionchetti P. Bacteria as the cause of ulcerative colitis. Gut. 2001; 48:132-5.
• [41]Kim SC, Tonkonogy SL, Albright CA, Tsang J, Balish EJ, Braun J et al.. Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology. 2005; 128:891-906.
• [42]Nakanishi Y, Sato T, Ohteki T. Commensal Gram-positive bacteria initiates colitis by inducing monocyte/macrophage mobilization. Mucosal Immunol. 2015; 8:152-60.
• [43]Noguchi M, Hiwatashi N, Liu ZX, Toyota T. Increased secretion of granulocyte-macrophage colony-stimulating factor in mucosal lesions of inflammatory bowel disease. Digestion. 2001; 63 Suppl 1:32-6.
• [44]Egea L, McAllister CS, Lakhdari O, Minev I, Shenouda S, Kagnoff MF. GM-CSF produced by nonhematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa. J Immunol. 2013; 190:1702-13.
• [45]Xu Y, Hunt NH, Bao S. The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation. Cell Res. 2008; 18:1220-9.
• [46]Sainathan SK, Hanna EM, Gong Q, Bishnupuri KS, Luo Q, Colonna M et al.. Granulocyte macrophage colony-stimulating factor ameliorates DSS-induced experimental colitis. Inflamm Bowel Dis. 2008; 14:88-99.
• [47]Segal AW. How neutrophils kill microbes. Annu Rev Immunol. 2005; 23:197-223.
• [48]Metzler KD, Fuchs TA, Nauseef WM, Reumaux D, Roesler J, Schulze I et al.. Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood. 2011; 117:953-9.
• [49]Meyer-Wentrup F, Benitez-Ribas D, Tacken PJ, Punt CJ, Figdor CG, de Vries IJ et al.. Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-α production. Blood. 2008; 111:4245-53.
• [50]Meyer-Wentrup F, Cambi A, Joosten B, Looman MW, de Vries IJ, Figdor CG et al.. DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production. J Leukoc Biol. 2009; 85:518-25.
• [51]Hutter J, Eriksson M, Johannssen T, Klopfleisch R, von Smolinski D, Gruber AD et al.. Role of the C-type lectin receptors MCL and DCIR in experimental colitis. PLoS One. 2014; 9:e103281.