The role of macrophages in inflammatory bowel diseases

Sigrid E.M. Heinsbroek; Siamon Gordon

doi:10.1017/S1462399409001069

The role of macrophages in inflammatory bowel diseases

Published online by Cambridge University Press: 14 May 2009

Sigrid E.M. Heinsbroek and

Siamon Gordon

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Sigrid E.M. Heinsbroek*: Affiliation:
Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Siamon Gordon: Affiliation:
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
*: *Corresponding author: Sigrid Heinsbroek, Department of Gastroenterology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5664109; Fax: +31 20 6917033; E-mail: s.e.heinsbroek@amc.uva.nl

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Abstract

The small and large intestine contain the largest number of macrophages in the body and these cells are strategically located directly underneath the epithelial layer, enabling them to sample the lumen. Such intestinal macrophages have a different phenotype from other tissue macrophages in that they ingest and may kill microbes but they do not mediate strong pro-inflammatory responses upon microbial recognition. These properties are essential for maintaining a healthy intestine. It is generally accepted that tolerance to the intestinal flora is lost in inflammatory bowel diseases, and genes involved in microbial recognition, killing and macrophage activation have already been associated with these diseases. In this review, we shed light on the intestinal macrophage and how it influences intestinal immunity.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e14

DOI: https://doi.org/10.1017/S1462399409001069 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2009

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References

1Gordon, S. (2008) Elie Metchnikoff: father of natural immunity. European Journal of Immunology 38, 3257-3264CrossRef Google Scholar PubMed

2Gordon, S. (2007) The macrophage: past, present and future. European Journal of Immunology 37 Supplement 1, S9-17CrossRef Google Scholar PubMed

3Podolsky, D.K. (2002) Inflammatory bowel disease. New Engand Journal of Medicine. 347, 417-429CrossRef Google Scholar PubMed

4Loftus, E.V. Jr, (2004) Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 126, 1504-1517CrossRef Google Scholar PubMed

5Coombes, J.L. and Powrie, F. (2008) Dendritic cells in intestinal immune regulation. Nature Reviews Immunology 8, 435-446CrossRef Google Scholar PubMed

6Ahern, P.P. et al. (2008) The interleukin-23 axis in intestinal inflammation. Immunological Reviews 226, 147-159CrossRef Google Scholar PubMed

7Brandtzaeg, P. et al. (2006) The B-cell system in inflammatory bowel disease. Advances in Experimental Medicine and Biology 579, 149-167Google Scholar

8Rijnierse, A. et al. (2007) Mast cells and nerves tickle in the tummy: Implications for inflammatory bowel disease and irritable bowel syndrome. Pharmacology & Therapeutics 116, 207-235CrossRef Google Scholar PubMed

9Hugot, J.P. et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599-603CrossRef Google Scholar PubMed

10Ogura, Y. et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603-606CrossRef Google Scholar PubMed

11Qualls, J.E. et al. (2006) Suppression of experimental colitis by intestinal mononuclear phagocytes. Journal of Leukocyte Biology 80, 802-815CrossRef Google Scholar PubMed

12Lee, S.H. et al. (1985) Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80. Journal of Experimental Medicine 161, 475-489Google Scholar

13Wahl, S.M. et al. (1987) Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proceedings of the National Academy of Sciences of the United States of America 84, 5788-5792CrossRef Google Scholar PubMed

14Smythies, L.E. et al. (2006) Mucosal IL-8 and TGF-beta recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells. Journal of Leukocyte Biology 80, 492-499CrossRef Google Scholar PubMed

15Crofton, R.W. et al. (1978) The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state. Journal of Experimental Medicine 148, 1-17Google Scholar

16Tarling, J.D. et al. (1987) Self-renewal of pulmonary alveolar macrophages: evidence from radiation chimera studies. Journal of Leukocyte Biology 42, 443-446CrossRef Google Scholar PubMed

17Geissmann, F. et al. (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71-82CrossRef Google Scholar PubMed

18Gordon, S. and Taylor, P.R. (2005) Monocyte and macrophage heterogeneity. Nature Reviews Immunology 5, 953-964CrossRef Google Scholar PubMed

19Smythies, L.E. et al. (2005) Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. Journal of Clinical Investigation 115, 66-75CrossRef Google Scholar PubMed

20Platt, A.M. and Mowat, A.M. (2008) Mucosal macrophages and the regulation of immune responses in the intestine. Immunology Letters 119, 22-31CrossRef Google Scholar PubMed

21Kuwata, H. et al. (2003) IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-alpha production in macrophages. Blood 102, 4123-4129CrossRef Google Scholar PubMed

22Randow, F. et al. (1995) Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. Journal of Experimental Medicine 181, 1887-1892CrossRef Google Scholar PubMed

23Schottelius, A.J. et al. (1999) Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. Journal of Biological Chemistry 274, 31868-31874CrossRef Google Scholar PubMed

24Naiki, Y. et al. (2005) Transforming growth factor-beta differentially inhibits MyD88-dependent, but not. Journal of Biological Chemistry 280, 5491-5495Google Scholar

25Kohn, R. et al. (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263-274CrossRef Google Scholar

26Shull, M.M. et al. (1992) Targeted disruption of the mouse transforming growth factor-[beta]1 gene results in multifocal inflammatory disease. Nature 359, 693-699CrossRef Google Scholar PubMed

27Schenk, M. et al. (2005) Macrophages expressing triggering receptor expressed on myeloid cells-1 are underrepresented in the human intestine. Journal of Immunology 174, 517-524Google Scholar

28Reterink, T.J. et al. (1996) Transforming growth factor-beta 1 (TGF-beta 1) down-regulates IgA Fc-receptor (CD89) expression on human monocytes. Clinical and Experimental Immunology 103, 161-166CrossRef Google Scholar PubMed

29Hogasen, A.K. et al. (1995) Transforming growth factor beta modulates C3 and factor B biosynthesis and complement receptor 3 expression in cultured human monocytes. Journal of Leukocyte Biology 57, 287-296CrossRef Google Scholar PubMed

30Willment, J.A. et al. (2003) Dectin-1 expression and function are enhanced on alternatively activated and GM-CSF-treated macrophages and are negatively regulated by IL-10, dexamethasone, and lipopolysaccharide. Journal of Immunology 171, 4569-4573CrossRef Google Scholar PubMed

31Martinez-Pomares, L. et al. (2003) Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies. Journal of Leukocyte Biology 73, 604-613CrossRef Google Scholar PubMed

32Spottl, T. et al. (2001) Monocyte differentiation in intestine-like macrophage phenotype induced by epithelial cells. Journal of Leukocyte Biology 70, 241-251CrossRef Google Scholar PubMed

33Jacob, S.S. et al. (2002) Monocyte-macrophage differentiation in vitro: modulation by extracellular matrix protein substratum. Molecular Cell Biochemistry 233, 9-17CrossRef Google Scholar PubMed

34Hedl, M. et al. (2007) Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proceedings of the National Academy of Sciences of the United States of America 104, 19440-19445CrossRef Google Scholar PubMed

35Rogler, G. et al. (1998) Isolation and phenotypic characterization of colonic macrophages. Clinical and Experimental Immunology 112, 205-215CrossRef Google Scholar PubMed

36Hausmann, M. et al. (2002) Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 122, 1987-2000Google Scholar

37Meng, G. et al. (2000) Lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and are the likely target cell for human immunodeficiency virus type 1 in the intestinal mucosa. Journal of Infectious Diseases 182, 785-791CrossRef Google Scholar

38Smith, P.D. et al. (2001) Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. Journal of Immunology 167, 2651-2656CrossRef Google Scholar PubMed

39Barclay, A.N. et al. (2002) CD200 and membrane protein interactions in the control of myeloid cells. Trends in Immunology 23, 285-290CrossRef Google Scholar PubMed

40Rugtveit, J. et al. (1994) Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut 35, 669-674CrossRef Google Scholar PubMed

41Burgio, V.L. et al. (1995) Peripheral monocyte and naive T-cell recruitment and activation in Crohn's disease. Gastroenterology 109, 1029-1038CrossRef Google Scholar PubMed

42Grimm, M.C. et al. (1995) Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa. Journal of Gastroenterology and Hepatology 10, 387-395Google Scholar

43Rugtveit, J. et al. (1997) Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD). Clinical and Experimental Immunology 110, 104-113CrossRef Google Scholar PubMed

44Schenk, M. et al. (2007) TREM-1–expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. Journal of Clinical Investigation 117, 3097-3106CrossRef Google Scholar PubMed

45Neurath, M.F. et al. (1998) Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease. Annals of the New York Academy of Sciences 859, 149-159Google Scholar

46Kamada, N. et al. (2008) Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. Journal of Clinical Investigation 118, 2269-2280Google Scholar

47Reinecker, H.C. et al. (1993) Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clinical and Experimental Immunology 94, 174-181CrossRef Google Scholar PubMed

48Reimund, J.M. et al. (1996) Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease. Gut 39, 684-689Google Scholar

49Naito, Y. et al. (2003) Enhanced intestinal inflammation induced by dextran sulfate sodium in tumor necrosis factor-alpha deficient mice. Journal of Gastroenterology and Hepatology. 18, 560-569CrossRef Google Scholar PubMed

50Tokuyama, H. et al. (2005) The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis. International Immunology 17, 1023-1034Google Scholar

51Sellon, R.K. et al. (1998) Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infection and Immunity 66, 5224-5231CrossRef Google Scholar PubMed

52Tannock, G.W. (2007) What immunologists should know about bacterial communities of the human bowel. Seminars in Immunology 19, 94-105CrossRef Google Scholar PubMed

53Rakoff-Nahoum, S. et al. (2004) Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis. Cell 118, 229-241CrossRef Google Scholar PubMed

54Atarashi, K. et al. (2008) ATP drives lamina propria TH17 cell differentiation. Nature 455, 808-812Google Scholar

55Elliott, D.E. et al. (2000) Does the failure to acquire helminthic parasites predispose to Crohn's disease? The FASEB Journal 14, 1848-1855CrossRef Google Scholar PubMed

56Wang, L.J. et al. (2008) Helminth infections and intestinal inflammation. World Journal of Gastroenterology. 14, 5125-5132Google Scholar

57Smith, P. et al. (2007) Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. Journal of Immunology 178, 4557-4566CrossRef Google Scholar

58Othman, M. et al. (2008) Alterations in intestinal microbial flora and human disease. Current Opinion in Gastroenterology 24, 11-16CrossRef Google Scholar PubMed

59Linskens, R.K. et al. (2001) The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scandinavian Journal of Gastroenterology Supplement, 29-40CrossRef Google Scholar PubMed

60Garrett, W.S. et al. (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131, 33-45CrossRef Google Scholar PubMed

61Mowat, A.M. (2003) Anatomical basis of tolerance and immunity to intestinal antigens. Nature Reviews Immunology 3, 331-341Google Scholar

62Rescigno, M. et al. (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunology 2, 361-367Google Scholar

63Sartor, R.B. (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577-594CrossRef Google Scholar PubMed

64Janeway, C.A. Jr, and Medzhitov, R. (2002) Innate immune recognition. Annual Review of Immunology 20, 197-216Google Scholar

65Lemaitre, B. et al. (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973-983Google Scholar

66Doyle, S.E. et al. (2004) Toll-like receptors induce a phagocytic gene program through p38. Journal of Experimental Medicine 199, 81-90CrossRef Google Scholar PubMed

67West, M.A. et al. (2004) Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science 305, 1153-1157CrossRef Google Scholar PubMed

68Blander, J.M. and Medzhitov, R. (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304, 1014-1018CrossRef Google Scholar PubMed

69Shiratsuchi, A. et al. (2004) Inhibitory effect of Toll-like receptor 4 on fusion between phagosomes and endosomes/lysosomes in macrophages. Journal of Immunology 172, 2039-2047CrossRef Google Scholar PubMed

70Akira, S. and Sato, S. (2003) Toll-like receptors and their signaling mechanisms. Scandinavian Journal of Infectious Diseases 35, 555-562CrossRef Google Scholar PubMed

71Muzio, M. et al. (2000) Toll like receptor family (TLT) and signalling pathway. European Cytokine Network 11, 489-490Google Scholar PubMed

72Ahmad-Nejad, P. et al. (2002) Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. European Journal of Immunology 32, 1958-1968Google Scholar

73Heil, F. et al. (2003) The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. European Journal of Immunology 33, 2987-2997CrossRef Google Scholar

74Latz, E. et al. (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nature Immunology 5, 190-198CrossRef Google Scholar PubMed

75Matsumoto, M. et al. (2003) Subcellular localization of Toll-like receptor 3 in human dendritic cells. Journal of Immunology 171, 3154-3162CrossRef Google Scholar PubMed

76Takeda, K. and Akira, S. (2005) Toll-like receptors in innate immunity. International Immunology 17, 1-14CrossRef Google Scholar PubMed

77Underhill, D.M. et al. (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401, 811-815CrossRef Google Scholar PubMed

78Cario, E. (2008) Therapeutic impact of toll-like receptors on inflammatory bowel diseases: a multiple-edged sword. Inflammatory Bowel Diseases 14, 411-421CrossRef Google Scholar PubMed

79Torok, H.P. et al. (2004) Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clinical Immunology 112, 85-91CrossRef Google Scholar PubMed

80Franchimont, D. et al. (2004) Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis. Gut 53, 987-992CrossRef Google Scholar PubMed

81Lodes, M.J. et al. (2004) Bacterial flagellin is a dominant antigen in Crohn disease. Journal of Clinical Investigation 113, 1296-1306CrossRef Google Scholar PubMed

82Vijay-Kumar, M. et al. (2007) Deletion of TLR5 results in spontaneous colitis in mice. Journal of Clinical Investigation 117, 3909-3921Google Scholar PubMed

83Shaw, M.H. et al. (2008) NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Current Opinion in Immunology 20, 377-382CrossRef Google Scholar PubMed

84Kobayashi, K.S. et al. (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731-734Google Scholar

85Ogura, Y. et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603-606CrossRef Google Scholar PubMed

86Hampe, J. et al. (2001) Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet 357, 1925-1928Google Scholar

87Inohara, N. et al. (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. Journal of Biological Chemistry 278, 5509-5512CrossRef Google Scholar PubMed

88Netea, M.G. et al. (2005) The Frameshift Mutation in Nod2 Results in Unresponsiveness Not Only to Nod2- but Also Nod1-activating Peptidoglycan Agonists. Journal of Biological Chemistry 280, 35859-35867CrossRef Google Scholar PubMed

89Maeda, S. et al. (2005) Nod2 Mutation in Crohn's Disease Potentiates NF-{kappa}B Activity and IL-1{beta} Processing. Science 307, 734-738CrossRef Google Scholar

90Li, J. et al. (2004) Regulation of IL-8 and IL-1{beta} expression in Crohn's disease associated NOD2/CARD15 mutations. Human Molecular Genetics 13, 1715-1725CrossRef Google Scholar PubMed

91Maeda, S. et al. (2005) Nod2 Mutation in Crohn's Disease Potentiates NF-{kappa}B Activity and IL-1{beta} Processing. Science 307, 734-738CrossRef Google Scholar

92Tremelling, M. et al. (2006) Complex insertion/deletion polymorphism in NOD1 (CARD4) is not associated with inflammatory bowel disease susceptibility in East Anglia panel. Inflammatory Bowel Diseases 12, 967-971CrossRef Google Scholar

93McGovern, D.P.B. et al. (2005) Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Human Molecular Genetics 14, 1245-1250CrossRef Google Scholar PubMed

94Franke, A. et al. (2006) No association between the functional CARD4 insertion/deletion polymorphism and inflammatory bowel diseases in the German population. Gut 55, 1679-1680CrossRef Google Scholar PubMed

95Zouali, H. et al. (2003) CARD4/NOD1 is not involved in inflammatory bowel disease. Gut 52, 71-74Google Scholar

96Van Limbergen, J. et al. (2007) Investigation of NOD1/CARD4 variation in inflammatory bowel disease using a haplotype-tagging strategy. Human Molecular Genetics 16, 2175-2186CrossRef Google Scholar PubMed

97Kummer, J.A. et al. (2007) Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response. Journal of Histochemistry and Cytochemistry 55, 443-452Google Scholar

98Boyden, E.D. and Dietrich, W.F. (2006) Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nature Genetics 38, 240-244CrossRef Google Scholar PubMed

99Faustin, B. et al. (2007) Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Molecular Cell 25, 713-724CrossRef Google Scholar PubMed

100Mariathasan, S. et al. (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228-232CrossRef Google Scholar PubMed

101Mariathasan, S. and Monack, D.M. (2007) Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nature Reviews Immunology 7, 31-40CrossRef Google Scholar PubMed

102Hoffman, H.M. et al. (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature Genetics 29, 301-305Google Scholar

103Agostini, L. et al. (2004) NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20, 319-325Google Scholar

104Villani, A.C. et al. (2009) Common variants in the NLRP3 region contribute to Crohn's disease susceptibility. Nature Genetics 41, 71-76CrossRef Google Scholar PubMed

105Zelensky, A.N. and Gready, J.E. (2005) The C-type lectin-like domain superfamily. FEBS Journal 272, 6179-6217CrossRef Google Scholar PubMed

106Ariizumi, K. et al. (2000) Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. Journal of Biological Chemistry 275, 20157-20167Google Scholar

107Brown, G.D. and Gordon, S. (2001) Immune recognition. A new receptor for beta-glucans. Nature 413, 36-37CrossRef Google Scholar PubMed

108Reid, D.M. et al. (2004) Expression of the {beta}-glucan receptor, Dectin-1, on murine leukocytes in situ correlates with its function in pathogen recognition and reveals potential roles in leukocyte interactions. Journal of Leukocyte Biology 76, 86-94CrossRef Google Scholar PubMed

109Brown, G.D. (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nature Reviews Immunology 6, 33-43Google Scholar

110LeibundGut-Landmann, S. et al. (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nature Immunology 8, 630-638Google Scholar

111Ariizumi, K. et al. (2000) Cloning of a Second Dendritic Cell-associated C-type Lectin (Dectin-2) and Its Alternatively Spliced Isoforms. Journal of Biological Chemistry 275, 11957-11963Google Scholar

112Taylor, P.R. et al. (2005) Dectin-2 is predominantly myeloid restricted and exhibits unique activation-dependent expression on maturing inflammatory monocytes elicited in vivo. European Journal of Immunology 35, 2163-2174CrossRef Google Scholar PubMed

113McGreal, E.P. et al. (2006) The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose. Glycobiology 16, 422-430Google Scholar

114Sato, K. et al. (2006) Dectin-2 Is a Pattern Recognition Receptor for Fungi That Couples with the Fc Receptor {gamma} Chain to Induce Innate Immune Responses. Journal of Biological Chemistry 281, 38854-38866CrossRef Google Scholar PubMed

115van Kooyk, Y. and Geijtenbeek, T.B.H. (2003) DC-SIGN: escape mechanism for pathogens. Nature Reviews Immunology 3, 697-709CrossRef Google Scholar PubMed

116Geijtenbeek, T.B. et al. (2003) Mycobacteria target DC-SIGN to suppress dendritic cell function. Journal of Experimental Medicine 197, 7-17Google Scholar

117Nunez, C. et al. (2007) CD209 in inflammatory bowel disease: a case-control study in the Spanish population. BMC Medical Genetics 8, 75CrossRef Google Scholar PubMed

118Gazi, U. and Martinez-Pomares, L.Influence of the mannose receptor in host immune responses. Immunobiology Jan 20; [Epub ahead of print]Google Scholar

119Heinsbroek, S.E. et al. (2008) Stage-specific sampling by pattern recognition receptors during Candida albicans phagocytosis. PLoS Pathogens 4, e1000218CrossRef Google Scholar PubMed

120Netea, M.G. et al. (2006) Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. Journal of Clinical Investigation 116, 1642-1650CrossRef Google Scholar PubMed

121Liu, L. et al. (2008) The beneficial effect of Rheum tanguticum polysaccharide on protecting against diarrhea, colonic inflammation and ulceration in rats with TNBS-induced colitis: the role of macrophage mannose receptor in inflammation and immune response. International Immunopharmacology 8, 1481-1492Google Scholar

122Aderem, A. and Underhill, D.M. (1999) Mechanisms of phagocytosis in macrophages. Annual Review of Immunology 17, 593-623CrossRef Google Scholar PubMed

123Stuart, L.M. and Ezekowitz, R.A. (2005) Phagocytosis: elegant complexity. Immunity 22, 539-550CrossRef Google Scholar PubMed

124Vieira, O.V. et al. (2002) Phagosome maturation: aging gracefully. Biochemical Journal 366, 689-704CrossRef Google Scholar PubMed

125Caradonna, L. et al. (2000) Phagocytosis, killing, lymphocyte-mediated antibacterial activity, serum autoantibodies, and plasma endotoxins in inflammatory bowel disease. American Journal of Gastroenterology. 95, 1495-1502CrossRef Google Scholar PubMed

126Hausmann, M. et al. (2001) Subtractive screening reveals up-regulation of NADPH oxidase expression in Crohn's disease intestinal macrophages. Clinical and Experimental Immunology 125, 48-55CrossRef Google Scholar PubMed

127Roberts, R.L. et al. (2008) Confirmation of association of IRGM and NCF4 with ileal Crohn's disease in a population-based cohort. Genes and Immunity 9, 561-565CrossRef Google Scholar

128Rioux, J.D. et al. (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genetics 39, 596-604CrossRef Google Scholar PubMed

129Krieglstein, C.F. et al. (2001) Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. Journal of Experimental Medicine 194, 1207-1218CrossRef Google Scholar PubMed

130Wang, M.H. et al. (2002) Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities. Scandinavian Journal of Immunology 56, 545-553Google Scholar

131Morrison, A.C. et al. (2004) Macrophage-stimulating protein, the ligand for the stem cell-derived tyrosine kinase/RON receptor tyrosine kinase, inhibits IL-12 production by primary peritoneal macrophages stimulated with IFN-gamma and lipopolysaccharide. Journal of Immunology 172, 1825-1832Google Scholar

132Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678CrossRef Google Scholar

133Fisher, S.A. et al. (2008) Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. Nature Genetics 40, 710-712CrossRef Google Scholar PubMed

134Kirkegaard, K. et al. (2004) Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nature Reviews Microbiology 2, 301-314Google Scholar

135Levine, B. and Yuan, J. (2005) Autophagy in cell death: an innocent convict? Journal of Clinical Investigation 115, 2679-2688CrossRef Google Scholar PubMed

136Sanjuan, M.A. et al. (2007) Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 450, 1253-1257Google Scholar

137Xu, Y. et al. (2007) Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27, 135-144Google Scholar

138Hampe, J. et al. (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nature Genetics 39, 207-211CrossRef Google Scholar PubMed

139Singh, S.B. et al. (2006) Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438-1441Google Scholar

140Kuballa, P. et al. (2008) Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLoS. ONE 3, e3391CrossRef Google Scholar PubMed

141Saitoh, T. et al. (2008) Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456, 264-268Google Scholar

142Cadwell, K. et al. (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456, 259-263CrossRef Google Scholar PubMed

143Baksh, F.K. et al. (2004) Absence of Mycobacterium avium subsp. paratuberculosis in the microdissected granulomas of Crohn's disease. Modern Pathology 17, 1289-1294CrossRef Google Scholar PubMed

144Ryan, P. et al. (2002) PCR detection of Mycobacterium paratuberculosis in Crohn's disease granulomas isolated by laser capture microdissection. Gut 51, 665-670CrossRef Google Scholar PubMed

145Helming, L. and Gordon, S. (2007) The molecular basis of macrophage fusion. Immunobiology 212, 785-793CrossRef Google Scholar PubMed

146Meconi, S. et al. (2007) Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro. Cellular Microbiology. 9, 1252-1261Google Scholar

147Kakazu, T. et al. (1999) Type 1 T-helper cell predominance in granulomas of Crohn's disease. American Journal of Gastroenterology 94, 2149-2155CrossRef Google Scholar PubMed

148Marks, D. and Segal, A. (2008) Innate immunity in inflammatory bowel disease: a disease hypothesis. Journal of Pathology 214, 260-266Google Scholar

149Smith, A.M. et al. Disordered macrophage cytokine secretion underlies impaired acute inflammation in Crohn's disease. Science (in press)Google Scholar

150Wirtz, S. and Neurath, M.F. (2007) Mouse models of inflammatory bowel disease. Advanced Drug Delivery Reviews 59, 1073-1083CrossRef Google Scholar PubMed

151Watanabe, N. et al. (2003) Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice. Digestive Diseases and Sciences 48, 408-414Google Scholar

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