1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Intestinal Mononuclear Phagocytes in Health and Disease

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • HTML
    123.58 Kb
  • PDF
    795.57 Kb
  • XML
    111.69 Kb
  • Authors: Theodore J. Sanders1, Ulf Yrlid2, Kevin J. Maloy3
  • Editor: Siamon Gordon4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Sir William Dunn School of Pathology, Oxford, OX1 3RE, United Kingdom; 2: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, S-405 30 Gothenburg, Sweden; 3: Sir William Dunn School of Pathology, Oxford, OX1 3RE, United Kingdom; 4: Oxford University, Oxford, United Kingdom
    • Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.MCHD-0047-2016
  • Received 09 August 2016 Accepted 30 November 2016 Published 20 January 2017
  • Kevin J. Maloy, [email protected]
image of Intestinal Mononuclear Phagocytes in Health and Disease
    Preview this microbiology spectrum article:
    Preview Magnify
    Zoom in
    Zoomout

    Intestinal Mononuclear Phagocytes in Health and Disease, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/5/1/MCHD-0047-2016-1.gif /docserver/preview/fulltext/microbiolspec/5/1/MCHD-0047-2016-2.gif

  • Abstract:

    The intestine is the tissue of the body with the highest constitutive exposure to foreign antigen and is also a common entry portal for many local and systemic pathogens. Therefore, the local immune system has the unenviable task of balancing efficient responses to dangerous pathogens with tolerance toward beneficial microbiota and food antigens. As in most tissues, the decision between tolerance and immunity is critically governed by the activity of local myeloid cells. However, the unique challenges posed by the intestinal environment have necessitated the development of several specialized mononuclear phagocyte populations with distinct phenotypic and functional characteristics that have vital roles in maintaining barrier function and immune homeostasis in the intestine. Intestinal mononuclear phagocyte populations, comprising dendritic cells and macrophages, are crucial for raising appropriate active immune responses against ingested pathogens. Recent technical advances, including microsurgical approaches allowing collection of cells migrating in intestinal lymph, intravital microscopy, and novel gene-targeting approaches, have led to clearer distinctions between mononuclear phagocyte populations in intestinal tissue. In this review, we present an overview of the various subpopulations of intestinal mononuclear phagocytes and discuss their phenotypic and functional characteristics. We also outline their roles in host protection from infection and their regulatory functions in maintaining immune tolerance toward beneficial intestinal antigens.

  • Citation: Sanders T, Yrlid U, Maloy K. 2017. Intestinal Mononuclear Phagocytes in Health and Disease. Microbiol Spectrum 5(1):MCHD-0047-2016. doi:10.1128/microbiolspec.MCHD-0047-2016.

References

1. Bradford BM, Sester DP, Hume DA, Mabbott NA. 2011. Defining the anatomical localisation of subsets of the murine mononuclear phagocyte system using integrin alpha X (Itgax, CD11c) and colony stimulating factor 1 receptor (Csf1r, CD115) expression fails to discriminate dendritic cells from macrophages. Immunobiology 216:1228–1237. [PubMed]
2. Schulz O, Jaensson E, Persson EK, Liu X, Worbs T, Agace WW, Pabst O. 2009. Intestinal CD103 +, but not CX3CR1 +, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J Exp Med 206:3101–3114. [PubMed]
3. Tamoutounour S, Henri S, Lelouard H, de Bovis B, de Haar C, van der Woude CJ, Woltman AM, Reyal Y, Bonnet D, Sichien D, Bain CC, Mowat AM, Reis e Sousa C, Poulin LF, Malissen B, Guilliams M. 2012. CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. Eur J Immunol 42:3150–3166. [PubMed]
4. Cerovic V, Houston SA, Scott CL, Aumeunier A, Yrlid U, Mowat AM, Milling SW. 2013. Intestinal CD103 – dendritic cells migrate in lymph and prime effector T cells. Mucosal Immunol 6:104–113. [PubMed]
5. Cerovic V, Bain CC, Mowat AM, Milling SW. 2014. Intestinal macrophages and dendritic cells: what’s the difference? Trends Immunol 35:270–277. [PubMed]
6. Watchmaker PB, Lahl K, Lee M, Baumjohann D, Morton J, Kim SJ, Zeng R, Dent A, Ansel KM, Diamond B, Hadeiba H, Butcher EC. 2014. Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice. Nat Immunol 15:98–108. [PubMed]
7. Jakubzick C, Bogunovic M, Bonito AJ, Kuan EL, Merad M, Randolph GJ. 2008. Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes. J Exp Med 205:2839–2850. [PubMed]
8. Denning TL, Norris BA, Medina-Contreras O, Manicassamy S, Geem D, Madan R, Karp CL, Pulendran B. 2011. Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J Immunol 187:733–747. [PubMed]
9. Fujimoto K, Karuppuchamy T, Takemura N, Shimohigoshi M, Machida T, Haseda Y, Aoshi T, Ishii KJ, Akira S, Uematsu S. 2011. A new subset of CD103 +CD8α + dendritic cells in the small intestine expresses TLR3, TLR7, and TLR9 and induces Th1 response and CTL activity. J Immunol 186:6287–6295. [PubMed]
10. Cerovic V, Houston SA, Westlund J, Utriainen L, Davison ES, Scott CL, Bain CC, Joeris T, Agace WW, Kroczek RA, Mowat AM, Yrlid U, Milling SW. 2015. Lymph-borne CD8α + dendritic cells are uniquely able to cross-prime CD8 + T cells with antigen acquired from intestinal epithelial cells. Mucosal Immunol 8:38–48. [PubMed]
11. Yrlid U, Cerovic V, Milling S, Jenkins CD, Klavinskis LS, MacPherson GG. 2006. A distinct subset of intestinal dendritic cells responds selectively to oral TLR7/8 stimulation. Eur J Immunol 36:2639–2648. [PubMed]
12. Bain CC, Scott CL, Uronen-Hansson H, Gudjonsson S, Jansson O, Grip O, Guilliams M, Malissen B, Agace WW, Mowat AM. 2013. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C hi monocyte precursors. Mucosal Immunol 6:498–510. [PubMed]
13. Satpathy AT, Briseño CG, Lee JS, Ng D, Manieri NA, Kc W, Wu X, Thomas SR, Lee WL, Turkoz M, McDonald KG, Meredith MM, Song C, Guidos CJ, Newberry RD, Ouyang W, Murphy TL, Stappenbeck TS, Gommerman JL, Nussenzweig MC, Colonna M, Kopan R, Murphy KM. 2013. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol 14:937–948. [PubMed]
14. Mann ER, Bernardo D, English NR, Landy J, Al-Hassi HO, Peake ST, Man R, Elliott TR, Spranger H, Lee GH, Parian A, Brant SR, Lazarev M, Hart AL, Li X, Knight SC. 2016. Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum. Gut 65:256–270. [PubMed]
15. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M, Liu K, Jakubzick C, Ingersoll MA, Leboeuf M, Stanley ER, Nussenzweig M, Lira SA, Randolph GJ, Merad M. 2009. Origin of the lamina propria dendritic cell network. Immunity 31:513–525. [PubMed]
16. Kinnebrew MA, Buffie CG, Diehl GE, Zenewicz LA, Leiner I, Hohl TM, Flavell RA, Littman DR, Pamer EG. 2012. Interleukin 23 production by intestinal CD103 +CD11b + dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36:276–287. [PubMed]
17. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y, Luche H, Fehling HJ, Hardt WD, Shakhar G, Jung S. 2009. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31:502–512. [PubMed]
18. Greter M, Helft J, Chow A, Hashimoto D, Mortha A, Agudo-Cantero J, Bogunovic M, Gautier EL, Miller J, Leboeuf M, Lu G, Aloman C, Brown BD, Pollard JW, Xiong H, Randolph GJ, Chipuk JE, Frenette PS, Merad M. 2012. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity 36:1031–1046. [PubMed]
19. Lewis KL, Caton ML, Bogunovic M, Greter M, Grajkowska LT, Ng D, Klinakis A, Charo IF, Jung S, Gommerman JL, Ivanov II, Liu K, Merad M, Reizis B. 2011. Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35:780–791. [PubMed]
20. Schlitzer A, McGovern N, Teo P, Zelante T, Atarashi K, Low D, Ho AW, See P, Shin A, Wasan PS, Hoeffel G, Malleret B, Heiseke A, Chew S, Jardine L, Purvis HA, Hilkens CM, Tam J, Poidinger M, Stanley ER, Krug AB, Renia L, Sivasankar B, Ng LG, Collin M, Ricciardi-Castagnoli P, Honda K, Haniffa M, Ginhoux F. 2013. IRF4 transcription factor-dependent CD11b + dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 38:970–983. [PubMed]
21. Persson EK, Uronen-Hansson H, Semmrich M, Rivollier A, Hägerbrand K, Marsal J, Gudjonsson S, Håkansson U, Reizis B, Kotarsky K, Agace WW. 2013. IRF4 transcription-factor-dependent CD103 +CD11b + dendritic cells drive mucosal T helper 17 cell differentiation. Immunity 38:958–969. [PubMed]
22. Edelson BT, Kc W, Juang R, Kohyama M, Benoit LA, Klekotka PA, Moon C, Albring JC, Ise W, Michael DG, Bhattacharya D, Stappenbeck TS, Holtzman MJ, Sung SS, Murphy TL, Hildner K, Murphy KM. 2010. Peripheral CD103 + dendritic cells form a unified subset developmentally related to CD8α + conventional dendritic cells. J Exp Med 207:823–836. [PubMed]
23. Luda KM, Joeris T, Persson EK, Rivollier A, Demiri M, Sitnik KM, Pool L, Holm JB, Melo-Gonzalez F, Richter L, Lambrecht BN, Kristiansen K, Travis MA, Svensson-Frej M, Kotarsky K, Agace WW. 2016. IRF8 transcription-factor-dependent classical dendritic cells are essential for intestinal T cell homeostasis. Immunity 44:860–874. [PubMed]
24. Schraml BU, van Blijswijk J, Zelenay S, Whitney PG, Filby A, Acton SE, Rogers NC, Moncaut N, Carvajal JJ, Reis e Sousa C. 2013. Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage. Cell 154:843–858. [PubMed]
25. Scott CL, Bain CC, Wright PB, Sichien D, Kotarsky K, Persson EK, Luda K, Guilliams M, Lambrecht BN, Agace WW, Milling SW, Mowat AM. 2015. CCR2 +CD103 – intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells. Mucosal Immunol 8:327–339. [PubMed]
26. Hägerbrand K, Westlund J, Yrlid U, Agace W, Johansson-Lindbom B. 2015. MyD88 signaling regulates steady-state migration of intestinal CD103 + dendritic cells independently of TNF-α and the gut microbiota. J Immunol 195:2888–2899. [PubMed]
27. Wilson NS, Young LJ, Kupresanin F, Naik SH, Vremec D, Heath WR, Akira S, Shortman K, Boyle J, Maraskovsky E, Belz GT, Villadangos JA. 2008. Normal proportion and expression of maturation markers in migratory dendritic cells in the absence of germs or Toll-like receptor signaling. Immunol Cell Biol 86:200–205. [PubMed]
28. Baratin M, Foray C, Demaria O, Habbeddine M, Pollet E, Maurizio J, Verthuy C, Davanture S, Azukizawa H, Flores-Langarica A, Dalod M, Lawrence T. 2015. Homeostatic NF-κB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance. Immunity 42:627–639. [PubMed]
29. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–258. [PubMed]
30. Chieppa M, Rescigno M, Huang AY, Germain RN. 2006. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med 203:2841–2852. [PubMed]
31. Farache J, Koren I, Milo I, Gurevich I, Kim KW, Zigmond E, Furtado GC, Lira SA, Shakhar G. 2013. Luminal bacteria recruit CD103 + dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. Immunity 38:581–595. [PubMed]
32. McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V, Knoop KA, Newberry RD, Miller MJ. 2012. Goblet cells deliver luminal antigen to CD103 + dendritic cells in the small intestine. Nature 483:345–349. [PubMed]
33. Shan M, Gentile M, Yeiser JR, Walland AC, Bornstein VU, Chen K, He B, Cassis L, Bigas A, Cols M, Comerma L, Huang B, Blander JM, Xiong H, Mayer L, Berin C, Augenlicht LH, Velcich A, Cerutti A. 2013. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342:447–453. [PubMed]
34. Mazzini E, Massimiliano L, Penna G, Rescigno M. 2014. Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1 + macrophages to CD103 + dendritic cells. Immunity 40:248–261. [PubMed]
35. Coombes JL, Siddiqui KR, Arancibia-Cárcamo CV, Hall J, Sun CM, Belkaid Y, Powrie F. 2007. A functionally specialized population of mucosal CD103 + DCs induces Foxp3 + regulatory T cells via a TGF-β- and retinoic acid-dependent mechanism. J Exp Med 204:1757–1764. [PubMed]
36. Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y. 2007. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204:1775–1785. [PubMed]
37. Jaensson-Gyllenbäck E, Kotarsky K, Zapata F, Persson EK, Gundersen TE, Blomhoff R, Agace WW. 2011. Bile retinoids imprint intestinal CD103 + dendritic cells with the ability to generate gut-tropic T cells. Mucosal Immunol 4:438–447. [PubMed]
38. Worthington JJ, Czajkowska BI, Melton AC, Travis MA. 2011. Intestinal dendritic cells specialize to activate transforming growth factor-β and induce Foxp3 + regulatory T cells via integrin αvβ8. Gastroenterology 141:1802–1812. [PubMed]
39. Johansson-Lindbom B, Svensson M, Pabst O, Palmqvist C, Marquez G, Förster R, Agace WW. 2005. Functional specialization of gut CD103 + dendritic cells in the regulation of tissue-selective T cell homing. J Exp Med 202:1063–1073. [PubMed]
40. Jaensson E, Uronen-Hansson H, Pabst O, Eksteen B, Tian J, Coombes JL, Berg PL, Davidsson T, Powrie F, Johansson-Lindbom B, Agace WW. 2008. Small intestinal CD103 + dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 205:2139–2149. [PubMed]
41. Matteoli G, Mazzini E, Iliev ID, Mileti E, Fallarino F, Puccetti P, Chieppa M, Rescigno M. 2010. Gut CD103 + dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction. Gut 59:595–604. [PubMed]
42. Worbs T, Bode U, Yan S, Hoffmann MW, Hintzen G, Bernhardt G, Förster R, Pabst O. 2006. Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J Exp Med 203:519–527. [PubMed]
43. Welty NE, Staley C, Ghilardi N, Sadowsky MJ, Igyártó BZ, Kaplan DH. 2013. Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism. J Exp Med 210:2011–2024. [PubMed]
44. Esterházy D, Loschko J, London M, Jove V, Oliveira TY, Mucida D. 2016. Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T reg cells and tolerance. Nat Immunol 17:545–555. [PubMed]
45. Rivollier A, He J, Kole A, Valatas V, Kelsall BL. 2012. Inflammation switches the differentiation program of Ly6C hi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J Exp Med 209:139–155. [PubMed]
46. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367. [PubMed]
47. Müller AJ, Kaiser P, Dittmar KE, Weber TC, Haueter S, Endt K, Songhet P, Zellweger C, Kremer M, Fehling HJ, Hardt WD. 2012. Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes. Cell Host Microbe 11:19–32. [PubMed]
48. Howe SE, Lickteig DJ, Plunkett KN, Ryerse JS, Konjufca V. 2014. The uptake of soluble and particulate antigens by epithelial cells in the mouse small intestine. PLoS One 9:e86656. doi:10.1371/journal.pone.0086656. [PubMed]
49. Platt AM, Bain CC, Bordon Y, Sester DP, Mowat AM. 2010. An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J Immunol 184:6843–6854. [PubMed]
50. Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, Friedlander G, Mack M, Shpigel N, Boneca IG, Murphy KM, Shakhar G, Halpern Z, Jung S. 2012. Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37:1076–1090. [PubMed]
51. Ueda Y, Kayama H, Jeon SG, Kusu T, Isaka Y, Rakugi H, Yamamoto M, Takeda K. 2010. Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10. Int Immunol 22:953–962. [PubMed]
52. Hadis U, Wahl B, Schulz O, Hardtke-Wolenski M, Schippers A, Wagner N, Müller W, Sparwasser T, Förster R, Pabst O. 2011. Intestinal tolerance requires gut homing and expansion of FoxP3 + regulatory T cells in the lamina propria. Immunity 34:237–246. [PubMed]
53. Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, Kronenberg M. 2009. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10:1178–1184. [PubMed]
54. Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Förster I, Akira S. 1999. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10:39–49. [PubMed]
55. Hirotani T, Lee PY, Kuwata H, Yamamoto M, Matsumoto M, Kawase I, Akira S, Takeda K. 2005. The nuclear IκB protein IκBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria. J Immunol 174:3650–3657. [PubMed]
56. Diehl GE, Longman RS, Zhang JX, Breart B, Galan C, Cuesta A, Schwab SR, Littman DR. 2013. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX 3CR1 hi cells. Nature 494:116–120. [PubMed]
57. Shaw MH, Kamada N, Kim YG, Núñez G. 2012. Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T H17 cells in the intestine. J Exp Med 209:251–258. [PubMed]
58. Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP, Belkaid Y, Merad M. 2014. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343:1249288. [PubMed]
59. Ginhoux F, Jung S. 2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14:392–404. [PubMed]
60. Bain CC, Bravo-Blas A, Scott CL, Gomez Perdiguero E, Geissmann F, Henri S, Malissen B, Osborne LC, Artis D, Mowat AM. 2014. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 15:929–937. [PubMed]
61. Auffray C, Fogg DK, Narni-Mancinelli E, Senechal B, Trouillet C, Saederup N, Leemput J, Bigot K, Campisi L, Abitbol M, Molina T, Charo I, Hume DA, Cumano A, Lauvau G, Geissmann F. 2009. CX3CR1 + CD115 + CD135 + common macrophage/DC precursors and the role of CX 3CR1 in their response to inflammation. J Exp Med 206:595–606. [PubMed]
62. Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L, Vizcay-Barrena G, Hedrick CC, Cook HT, Diebold S, Geissmann F. 2013. Nr4a1-dependent Ly6C low monocytes monitor endothelial cells and orchestrate their disposal. Cell 153:362–375. [PubMed]
63. Takada Y, Hisamatsu T, Kamada N, Kitazume MT, Honda H, Oshima Y, Saito R, Takayama T, Kobayashi T, Chinen H, Mikami Y, Kanai T, Okamoto S, Hibi T. 2010. Monocyte chemoattractant protein-1 contributes to gut homeostasis and intestinal inflammation by composition of IL-10-producing regulatory macrophage subset. J Immunol 184:2671–2676. [PubMed]
64. Serbina NV, Pamer EG. 2006. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7:311–317. [PubMed]
65. MacDonald KP, Palmer JS, Cronau S, Seppanen E, Olver S, Raffelt NC, Kuns R, Pettit AR, Clouston A, Wainwright B, Branstetter D, Smith J, Paxton RJ, Cerretti DP, Bonham L, Hill GR, Hume DA. 2010. An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation. Blood 116:3955–3963. [PubMed]
66. Olson MC, Scott EW, Hack AA, Su GH, Tenen DG, Singh H, Simon MC. 1995. PU.1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation. Immunity 3:703–714. [PubMed]
67. Bain CC, Mowat AM. 2014. The monocyte-macrophage axis in the intestine. Cell Immunol 291:41–48. [PubMed]
68. Mahida YR, Wu KC, Jewell DP. 1989. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut 30:1362–1370. [PubMed]
69. Smythies LE, Sellers M, Clements RH, Mosteller-Barnum M, Meng G, Benjamin WH, Orenstein JM, Smith PD. 2005. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 115:66–75. [PubMed]
70. Smythies LE, Shen R, Bimczok D, Novak L, Clements RH, Eckhoff DE, Bouchard P, George MD, Hu WK, Dandekar S, Smith PD. 2010. Inflammation anergy in human intestinal macrophages is due to Smad-induced IκBα expression and NF-κB inactivation. J Biol Chem 285:19593–19604. [PubMed]
71. Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, Sakuraba A, Kitazume MT, Sugita A, Koganei K, Akagawa KS, Hibi T. 2008. Unique CD14 + intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. J Clin Invest 118:2269–2280.
72. Grimm MC, Pavli P, Van de Pol E, Doe WF. 1995. Evidence for a CD14 + population of monocytes in inflammatory bowel disease mucosa—implications for pathogenesis. Clin Exp Immunol 100:291–297. [PubMed]
73. Grimm MC, Pullman WE, Bennett GM, Sullivan PJ, Pavli P, Doe WF. 1995. Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa. J Gastroenterol Hepatol 10:387–395. [PubMed]
74. Weber B, Saurer L, Schenk M, Dickgreber N, Mueller C. 2011. CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions. Eur J Immunol 41:773–779. [PubMed]
75. Qualls JE, Kaplan AM, van Rooijen N, Cohen DA. 2006. Suppression of experimental colitis by intestinal mononuclear phagocytes. J Leukoc Biol 80:802–815. [PubMed]
76. Pull SL, Doherty JM, Mills JC, Gordon JI, Stappenbeck TS. 2005. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc Natl Acad Sci U S A 102:99–104. [PubMed]
77. Seo SU, Kamada N, Muñoz-Planillo R, Kim YG, Kim D, Koizumi Y, Hasegawa M, Himpsl SD, Browne HP, Lawley TD, Mobley HL, Inohara N, Núñez G. 2015. Distinct commensals induce interleukin-1β via NLRP3 inflammasome in inflammatory monocytes to promote intestinal inflammation in response to injury. Immunity 42:744–755. [PubMed]
78. Dunay IR, Damatta RA, Fux B, Presti R, Greco S, Colonna M, Sibley LD. 2008. Gr1 + inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity 29:306–317. [PubMed]
79. Schulthess J, Meresse B, Ramiro-Puig E, Montcuquet N, Darche S, Bègue B, Ruemmele F, Combadière C, Di Santo JP, Buzoni-Gatel D, Cerf-Bensussan N. 2012. Interleukin-15-dependent NKp46 + innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes. Immunity 37:108–121. [PubMed]
80. Manta C, Heupel E, Radulovic K, Rossini V, Garbi N, Riedel CU, Niess JH. 2013. CX 3CR1 + macrophages support IL-22 production by innate lymphoid cells during infection with Citrobacter rodentium. Mucosal Immunol 6:177–188. [PubMed]
81. Longman RS, Diehl GE, Victorio DA, Huh JR, Galan C, Miraldi ER, Swaminath A, Bonneau R, Scherl EJ, Littman DR. 2014. CX 3CR1 + mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. J Exp Med 211:1571–1583. [PubMed]
82. deSchoolmeester ML, Little MC, Rollins BJ, Else KJ. 2003. Absence of CC chemokine ligand 2 results in an altered Th1/Th2 cytokine balance and failure to expel Trichuris muris infection. J Immunol 170:4693–4700. [PubMed]
83. Anthony RM, Urban JF, Jr, Alem F, Hamed HA, Rozo CT, Boucher JL, Van Rooijen N, Gause WC. 2006. Memory T H2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat Med 12:955–960. [PubMed]
84. Grainger JR, Wohlfert EA, Fuss IJ, Bouladoux N, Askenase MH, Legrand F, Koo LY, Brenchley JM, Fraser ID, Belkaid Y. 2013. Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat Med 19:713–721. [PubMed]
85. Takayama T, Kamada N, Chinen H, Okamoto S, Kitazume MT, Chang J, Matuzaki Y, Suzuki S, Sugita A, Koganei K, Hisamatsu T, Kanai T, Hibi T. 2010. Imbalance of NKp44 +NKp46 – and NKp44 –NKp46 + natural killer cells in the intestinal mucosa of patients with Crohn’s disease. Gastroenterology 139:882–892, 892.e1–892.e3. doi:10.1053/j.gastro.2010.05.040.
86. Kamada N, Hisamatsu T, Honda H, Kobayashi T, Chinen H, Takayama T, Kitazume MT, Okamoto S, Koganei K, Sugita A, Kanai T, Hibi T. 2010. TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn’s disease. Inflamm Bowel Dis 16:568–575. [PubMed]
87. Uo M, Hisamatsu T, Miyoshi J, Kaito D, Yoneno K, Kitazume MT, Mori M, Sugita A, Koganei K, Matsuoka K, Kanai T, Hibi T. 2013. Mucosal CXCR4 + IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation. Gut 62:1734–1744. [PubMed]
88. Schenk M, Bouchon A, Birrer S, Colonna M, Mueller C. 2005. Macrophages expressing triggering receptor expressed on myeloid cells-1 are underrepresented in the human intestine. J Immunol 174:517–524. [PubMed]
89. Schenk M, Bouchon A, Seibold F, Mueller C. 2007. TREM-1-expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. J Clin Invest 117:3097–3106. [PubMed]
90. Rugtveit J, Haraldsen G, Høgåsen AK, Bakka A, Brandtzaeg P, Scott H. 1995. Respiratory burst of intestinal macrophages in inflammatory bowel disease is mainly caused by CD14 +L1 + monocyte derived cells. Gut 37:367–373. [PubMed]
91. Nathan C, Cunningham-Bussel A. 2013. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol 13:349–361. [PubMed]
92. Nakagawara A, Nathan CF, Cohn ZA. 1981. Hydrogen peroxide metabolism in human monocytes during differentiation in vitro. J Clin Invest 68:1243–1252. [PubMed]
93. Kamada N, Hisamatsu T, Honda H, Kobayashi T, Chinen H, Kitazume MT, Takayama T, Okamoto S, Koganei K, Sugita A, Kanai T, Hibi T. 2009. Human CD14 + macrophages in intestinal lamina propria exhibit potent antigen-presenting ability. J Immunol 183:1724–1731. [PubMed]
94. Caradonna L, Amati L, Lella P, Jirillo E, Caccavo D. 2000. Phagocytosis, killing, lymphocyte-mediated antibacterial activity, serum autoantibodies, and plasma endotoxins in inflammatory bowel disease. Am J Gastroenterol 95:1495–1502. [PubMed]
95. Smith AM, Rahman FZ, Hayee B, Graham SJ, Marks DJ, Sewell GW, Palmer CD, Wilde J, Foxwell BM, Gloger IS, Sweeting T, Marsh M, Walker AP, Bloom SL, Segal AW. 2009. Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn’s disease. J Exp Med 206:1883–1897. [PubMed]
96. Marks DJ, Miyagi K, Rahman FZ, Novelli M, Bloom SL, Segal AW. 2009. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am J Gastroenterol 104:117–124. [PubMed]
97. Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S. 2008. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol 9:769–776. [PubMed]
98. Cerovic V, Jenkins CD, Barnes AG, Milling SW, MacPherson GG, Klavinskis LS. 2009. Hyporesponsiveness of intestinal dendritic cells to TLR stimulation is limited to TLR4. J Immunol 182:2405–2415. [PubMed]
99. Laffont S, Siddiqui KR, Powrie F. 2010. Intestinal inflammation abrogates the tolerogenic properties of MLN CD103 + dendritic cells. Eur J Immunol 40:1877–1883. [PubMed]
100. Aychek T, Mildner A, Yona S, Kim KW, Lampl N, Reich-Zeliger S, Boon L, Yogev N, Waisman A, Cua DJ, Jung S. 2015. IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology. Nat Commun 6:6525. doi:10.1038/ncomms7525.
101. Hart AL, Al-Hassi HO, Rigby RJ, Bell SJ, Emmanuel AV, Knight SC, Kamm MA, Stagg AJ. 2005. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 129:50–65. [PubMed]
102. Baumgart DC, Thomas S, Przesdzing I, Metzke D, Bielecki C, Lehmann SM, Lehnardt S, Dörffel Y, Sturm A, Scheffold A, Schmitz J, Radbruch A. 2009. Exaggerated inflammatory response of primary human myeloid dendritic cells to lipopolysaccharide in patients with inflammatory bowel disease. Clin Exp Immunol 157:423–436. [PubMed]
103. Bell SJ, Rigby R, English N, Mann SD, Knight SC, Kamm MA, Stagg AJ. 2001. Migration and maturation of human colonic dendritic cells. J Immunol 166:4958–4967. [PubMed]
104. Sakuraba A, Sato T, Kamada N, Kitazume M, Sugita A, Hibi T. 2009. Th1/Th17 immune response is induced by mesenteric lymph node dendritic cells in Crohn’s disease. Gastroenterology 137:1736–1745. [PubMed]
105. Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, Fiocchi C, Strober W. 1996. Disparate CD4 + lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-γ, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 157:1261–1270. [PubMed]
106. Sanders TJ, McCarthy NE, Giles EM, Davidson KL, Haltalli ML, Hazell S, Lindsay JO, Stagg AJ. 2014. Increased production of retinoic acid by intestinal macrophages contributes to their inflammatory phenotype in patients with Crohn’s disease. Gastroenterology 146:1278–88.e2. doi:10.1053/j.gastro.2014.01.057.
107. Magnusson MK, Brynjólfsson SF, Dige A, Uronen-Hansson H, Börjesson LG, Bengtsson JL, Gudjonsson S, Öhman L, Agnholt J, Sjövall H, Agace WW, Wick MJ. 2016. Macrophage and dendritic cell subsets in IBD: ALDH + cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation. Mucosal Immunol 9:171–182. [PubMed]
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016
2017-01-20
2021-04-21

Abstract:

The intestine is the tissue of the body with the highest constitutive exposure to foreign antigen and is also a common entry portal for many local and systemic pathogens. Therefore, the local immune system has the unenviable task of balancing efficient responses to dangerous pathogens with tolerance toward beneficial microbiota and food antigens. As in most tissues, the decision between tolerance and immunity is critically governed by the activity of local myeloid cells. However, the unique challenges posed by the intestinal environment have necessitated the development of several specialized mononuclear phagocyte populations with distinct phenotypic and functional characteristics that have vital roles in maintaining barrier function and immune homeostasis in the intestine. Intestinal mononuclear phagocyte populations, comprising dendritic cells and macrophages, are crucial for raising appropriate active immune responses against ingested pathogens. Recent technical advances, including microsurgical approaches allowing collection of cells migrating in intestinal lymph, intravital microscopy, and novel gene-targeting approaches, have led to clearer distinctions between mononuclear phagocyte populations in intestinal tissue. In this review, we present an overview of the various subpopulations of intestinal mononuclear phagocytes and discuss their phenotypic and functional characteristics. We also outline their roles in host protection from infection and their regulatory functions in maintaining immune tolerance toward beneficial intestinal antigens.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/microbiolspec/5/1/MCHD-0047-2016.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016&mimeType=html&fmt=ahah

Figures

Intestinal Mononuclear Phagocytes in Health and Disease
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-1,webId=/content/author/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-1,properties={foaf_givenname=Theodore J., foaf_name=Theodore J. Sanders, foaf_surname=Sanders, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-2,webId=/content/author/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-2,properties={foaf_givenname=Ulf, foaf_name=Ulf Yrlid, foaf_surname=Yrlid, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-aff2]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-3,webId=/content/author/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-3,properties={foaf_givenname=Kevin J., foaf_name=Kevin J. Maloy, foaf_surname=Maloy, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016-aff3]]}]]
Citation: Sanders T, Yrlid U, Maloy K. 2017. Intestinal mononuclear phagocytes in health and disease. microbiolspec 5(1): doi:10.1128/microbiolspec.MCHD-0047-2016
/content/microbiolspec/10.1128/microbiolspec.MCHD-0047-2016.fig1
FIGURE 1
Major subsets of murine mononuclear phagocytes. In the steady-state intestine, resident Mɸ and migratory DCs act synergistically to maintain homeostasis and prevent inflammation. In response to infectious or inflammatory insults, recruited Ly6C monocytes and migratory DCs exhibit a proinflammatory phenotype that coordinates protective innate and adaptive immune responses. However, sustained activation of mononuclear phagocytes can drive chronic intestinal inflammation, leading to tissue damage and impaired function. CTL, cytotoxic T lymphocyte; NO, nitric oxide.
microbiolspec/5/1/MCHD-0047-2016-fig1_thmb.gif
microbiolspec/5/1/MCHD-0047-2016-fig1.gif
Image of FIGURE 1

Click to view

FIGURE 1

Major subsets of murine mononuclear phagocytes. In the steady-state intestine, resident Mɸ and migratory DCs act synergistically to maintain homeostasis and prevent inflammation. In response to infectious or inflammatory insults, recruited Ly6C monocytes and migratory DCs exhibit a proinflammatory phenotype that coordinates protective innate and adaptive immune responses. However, sustained activation of mononuclear phagocytes can drive chronic intestinal inflammation, leading to tissue damage and impaired function. CTL, cytotoxic T lymphocyte; NO, nitric oxide.

Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.MCHD-0047-2016
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error