Advertisement

Seminars in Immunopathology

, Volume 35, Issue 5, pp 541–552 | Cite as

Macrophage heterogeneity in lymphoid tissues

  • Joke M. M. den HaanEmail author
  • Luisa Martinez-PomaresEmail author
Review

Abstract

Macrophages in lymphoid organs exhibit a wide variety of phenotypes and functions. These cells excel in the removal of apoptotic cells that arise during the generation of immune cells and are thereby essential for the prevention of auto-immune responses. In addition to this macrophages in the secondary lymphoid organs form an important barrier for spreading of infections by phagocytosis of pathogens and the activation of both innate and adaptive immune responses. Thus, the remarkable ability of macrophages to phagocytose and handle a wide range of self and non-self material and to produce immunomediators is effectively exploited within lymphoid organs to regulate immune activation.

Keywords

Macrophages Lymph nodes Spleen Bone marrow Thyroid Haematopoiesis Apoptotic cell recognition Antigen presentation Immune activation 

Notes

Acknowledgments

J.M.M.d.H. is supported by grants from the Dutch Scientific Research program (NWO grants 836.08.003) and the Dutch Cancer Society (VU2009-4504). L. M-P is supported by the University of Nottingham.

References

  1. 1.
    Hume DA (2011) Applications of myeloid-specific promoters in transgenic mice support in vivo imaging and functional genomics but do not support the concept of distinct macrophage and dendritic cell lineages or roles in immunity. J Leukoc Biol 89(4):525–538Google Scholar
  2. 2.
    Chow A, Brown BD, Merad M (2011) Studying the mononuclear phagocyte system in the molecular age. Nat Rev Immunol 11(11):788–798Google Scholar
  3. 3.
    Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174(1–2):83–93PubMedCrossRefGoogle Scholar
  4. 4.
    Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, Poulton IJ, van Rooijen N, Alexander KA, Raggatt LJ, Levesque JP (2010) Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 116(23):4815–4828. doi: 10.1182/blood-2009-11-253534 PubMedCrossRefGoogle Scholar
  5. 5.
    Chow A, Lucas D, Hidalgo A, Mendez-Ferrer S, Hashimoto D, Scheiermann C, Battista M, Leboeuf M, Prophete C, Van RN, Tanaka M, Merad M, Frenette PS (2011) Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 208(2):261–271Google Scholar
  6. 6.
    Ehninger A, Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. The Journal of experimental medicine 208(3):421–428. doi: 10.1084/jem.20110132 PubMedCrossRefGoogle Scholar
  7. 7.
    Ludin A, Itkin T, Gur-Cohen S, Mildner A, Shezen E, Golan K, Kollet O, Kalinkovich A, Porat Z, D’Uva G, Schajnovitz A, Voronov E, Brenner DA, Apte RN, Jung S, Lapidot T (2012) Monocytes–macrophages that express alpha-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow. Nat Immunol 13(11):1072–1082. doi: 10.1038/ni.2408 PubMedCrossRefGoogle Scholar
  8. 8.
    Surh CD, Sprent J (1994) T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372(6501):100–103PubMedCrossRefGoogle Scholar
  9. 9.
    Hume DA, Robinson AP, MacPherson GG, Gordon S (1983) The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs. J Exp Med 158(5):1522–1536PubMedCrossRefGoogle Scholar
  10. 10.
    Linehan SA, Martinez-Pomares L, Stahl PD, Gordon S (1999) Mannose receptor and its putative ligands in normal murine lymphoid and nonlymphoid organs: in situ expression of mannose receptor by selected macrophages, endothelial cells, perivascular microglia, and mesangial cells, but not dendritic cells. J Exp Med 189(12):1961–1972PubMedCrossRefGoogle Scholar
  11. 11.
    Cecchini MG, Dominguez MG, Mocci S, Wetterwald A, Felix R, Fleisch H, Chisholm O, Hofstetter W, Pollard JW, Stanley ER (1994) Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development 120(6):1357–1372PubMedGoogle Scholar
  12. 12.
    Kim HJ, Alonzo ES, Dorothee G, Pollard JW, Sant’Angelo DB (2010) Selective depletion of eosinophils or neutrophils in mice impacts the efficiency of apoptotic cell clearance in the thymus. PloS One 5(7):e11439Google Scholar
  13. 13.
    Schulz C, Gomez PE, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336(6077):86–90Google Scholar
  14. 14.
    Ravichandran KS (2011) Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity 35 (4):445–455Google Scholar
  15. 15.
    Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, Earp HS, Matsushima GK (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411(6834):207–211PubMedCrossRefGoogle Scholar
  16. 16.
    Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417(6885):182–187PubMedCrossRefGoogle Scholar
  17. 17.
    Hanayama R, Tanaka M, Miwa K, Nagata S (2004) Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. J Immunol 172(6):3876–3882PubMedGoogle Scholar
  18. 18.
    Platt N, Suzuki H, Kodama T, Gordon S (2000) Apoptotic thymocyte clearance in scavenger receptor class A-deficient mice is apparently normal. J Immunol 164(9):4861–4867PubMedGoogle Scholar
  19. 19.
    Platt N, Suzuki H, Kurihara Y, Kodama T, Gordon S (1996) Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro. Proc Natl Acad Sci USA 93(22):12456–12460PubMedCrossRefGoogle Scholar
  20. 20.
    Ram S, Lewis LA, Rice PA (2010) Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev 23(4):740–780Google Scholar
  21. 21.
    Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S, Helft J, Chow A, Elpek KG, Gordonov S, Mazloom AR, Ma’ayan A, Chua WJ, Hansen TH, Turley SJ, Merad M, Randolph GJ, Gautier EL, Jakubzick C, Randolph GJ, Best AJ, Knell J, Goldrath A, Miller J, Brown B, Merad M, Jojic V, Koller D, Cohen N, Brennan P, Brenner M, Shay T, Regev A, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S, Jianu R, Laidlaw D, Collins J, Narayan K, Sylvia K, Kang J, Gazit R, Garrison BS, Rossi DJ, Kim F, Rao TN, Wagers A, Shinton SA, Hardy RR, Monach P, Bezman NA, Sun JC, Kim CC, Lanier LL, Heng T, Kreslavsky T, Painter M, Ericson J, Davis S, Mathis D, Benoist C (2012) Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13:1118–1128Google Scholar
  22. 22.
    Kohyama M, Ise W, Edelson BT, Wilker PR, Hildner K, Mejia C, Frazier WA, Murphy TL, Murphy KM (2009) Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457(7227):318–321PubMedCrossRefGoogle Scholar
  23. 23.
    Ganz T (2012) Macrophages and systemic iron homeostasis. J Innate Immun 4(5–6):446–453Google Scholar
  24. 24.
    Zhang Z, Zhang F, An P, Guo X, Shen Y, Tao Y, Wu Q, Zhang Y, Yu Y, Ning B, Nie G, Knutson MD, Anderson GJ, Wang F (2011) Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood 118(7):1912–1922Google Scholar
  25. 25.
    Soe-Lin S, Apte SS, Andriopoulos B Jr, Andrews MC, Schranzhofer M, Kahawita T, Garcia-Santos D, Ponka P (2009) Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc Natl Acad Sci U S A 106(14):5960–5965PubMedCrossRefGoogle Scholar
  26. 26.
    Kovtunovych G, Eckhaus MA, Ghosh MC, Ollivierre-Wilson H, Rouault TA (2010) Dysfunction of the heme recycling system in heme oxygenase 1-deficient mice: effects on macrophage viability and tissue iron distribution. Blood 116(26):6054–6062Google Scholar
  27. 27.
    Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409(6817):198–201PubMedCrossRefGoogle Scholar
  28. 28.
    Oldenborg PA, Zheleznyak A, Fang YF, Lagenaur CF, Gresham HD, Lindberg FP (2000) Role of CD47 as a marker of self on red blood cells. Science 288(5473):2051–2054PubMedCrossRefGoogle Scholar
  29. 29.
    Burger P, Hilarius-Stokman P, de Korte D, van den Berg TK, van Bruggen R (2012) CD47 functions as a molecular switch for erythrocyte phagocytosis. Blood 119(23):5512–5521Google Scholar
  30. 30.
    Hemmi H, Idoyaga J, Suda K, Suda N, Kennedy K, Noda M, Aderem A, Steinman RM (2009) A new triggering receptor expressed on myeloid cells (Trem) family member, Trem-like 4, binds to dead cells and is a DNAX activation protein 12-linked marker for subsets of mouse macrophages and dendritic cells. J Immunol 182(3):1278–1286PubMedGoogle Scholar
  31. 31.
    Kurotaki D, Kon S, Bae K, Ito K, Matsui Y, Nakayama Y, Kanayama M, Kimura C, Narita Y, Nishimura T, Iwabuchi K, Mack M, van Rooijen N, Sakaguchi S, Uede T, Morimoto J (2011) CSF-1-dependent red pulp macrophages regulate CD4 T cell responses. J Immunol 186(4):2229–2237Google Scholar
  32. 32.
    Martinez-Pomares L (2012) The mannose receptor. J Leukoc Biol 92(6):1177–1186. doi: 10.1189/jlb.0512231 PubMedCrossRefGoogle Scholar
  33. 33.
    Akilov OE, Kasuboski RE, Carter CR, McDowell MA (2007) The role of mannose receptor during experimental leishmaniasis. J Leukoc Biol 81(5):1188–1196PubMedCrossRefGoogle Scholar
  34. 34.
    Lee SJ, Zheng NY, Clavijo M, Nussenzweig MC (2003) Normal host defense during systemic candidiasis in mannose receptor-deficient mice. Infect Immun 71(1):437–445PubMedCrossRefGoogle Scholar
  35. 35.
    Lee SJ, Evers S, Roeder D, Parlow AF, Risteli J, Risteli L, Lee YC, Feizi T, Langen H, Nussenzweig MC (2002) Mannose receptor-mediated regulation of serum glycoprotein homeostasis. Science 295(5561):1898–1901PubMedCrossRefGoogle Scholar
  36. 36.
    Marttila-Ichihara F, Turja R, Miiluniemi M, Karikoski M, Maksimow M, Niemela J, Martinez-Pomares L, Salmi M, Jalkanen S (2008) Macrophage mannose receptor on lymphatics controls cell trafficking. Blood 112(1):64–72PubMedCrossRefGoogle Scholar
  37. 37.
    Mebius RE, Kraal G (2005) Structure and function of the spleen. Nat Rev Immunol 5(8):606–616. doi: 10.1038/nri1669 PubMedCrossRefGoogle Scholar
  38. 38.
    Klaas M, Crocker PR (2012) Sialoadhesin in recognition of self and non-self. Semin Immunopathol 34(3):353–364. doi: 10.1007/s00281-012-0310-3 PubMedCrossRefGoogle Scholar
  39. 39.
    Berney C, Herren S, Power CA, Gordon S, Martinez-Pomares L, Kosco-Vilbois MH (1999) A member of the dendritic cell family that enters B cell follicles and stimulates primary antibody responses identified by a mannose receptor fusion protein. J Exp Med 190(6):851–860PubMedCrossRefGoogle Scholar
  40. 40.
    Martinez-Pomares L, Kosco-Vilbois M, Darley E, Tree P, Herren S, Bonnefoy JY, Gordon S (1996) Fc chimeric protein containing the cysteine-rich domain of the murine mannose receptor binds to macrophages from splenic marginal zone and lymph node subcapsular sinus and to germinal centers. J Exp Med 184(5):1927–1937PubMedCrossRefGoogle Scholar
  41. 41.
    Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA, Boes M, Fink K, Henrickson SE, Shayakhmetov DM, Di Paolo NC, van Rooijen N, Mempel TR, Whelan SP, von Andrian UH (2007) Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450(7166):110–114. doi: 10.1038/nature06287 PubMedCrossRefGoogle Scholar
  42. 42.
    Phan TG, Green JA, Gray EE, Xu Y, Cyster JG (2009) Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nat Immunol 10(7):786–793. doi: 10.1038/ni.1745 PubMedCrossRefGoogle Scholar
  43. 43.
    Phan TG, Grigorova I, Okada T, Cyster JG (2007) Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat Immunol 8(9):992–1000. doi: 10.1038/ni1494 PubMedCrossRefGoogle Scholar
  44. 44.
    Carrasco YR, Batista FD (2007) B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 27(1):160–171. doi: 10.1016/j.immuni.2007.06.007 PubMedCrossRefGoogle Scholar
  45. 45.
    Honke N, Shaabani N, Cadeddu G, Sorg UR, Zhang DE, Trilling M, Klingel K, Sauter M, Kandolf R, Gailus N, van Rooijen N, Burkart C, Baldus SE, Grusdat M, Lohning M, Hengel H, Pfeffer K, Tanaka M, Haussinger D, Recher M, Lang PA, Lang KS (2012) Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nat Immunol 13(1):51–57. doi: 10.1038/ni.2169 CrossRefGoogle Scholar
  46. 46.
    Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM (2008) Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322(5904):1097–1100PubMedCrossRefGoogle Scholar
  47. 47.
    Backer R, Schwandt T, Greuter M, Oosting M, Jungerkes F, Tuting T, Boon L, O’Toole T, Kraal G, Limmer A, den Haan JM (2010) Effective collaboration between marginal metallophilic macrophages and CD8+ dendritic cells in the generation of cytotoxic T cells. Proc Natl Acad Sci U S A 107(1):216–221. doi: 10.1073/pnas.0909541107 PubMedCrossRefGoogle Scholar
  48. 48.
    Iannacone M, Moseman EA, Tonti E, Bosurgi L, Junt T, Henrickson SE, Whelan SP, Guidotti LG, von Andrian UH (2010) Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature 465(7301):1079–1083. doi: 10.1038/nature09118 PubMedCrossRefGoogle Scholar
  49. 49.
    Schwandt T, Schumak B, Gielen GH, Jungerkes F, Schmidbauer P, Klocke K, Staratschek-Jox A, van Rooijen N, Kraal G, Ludwig-Portugall I, Franken L, Wehner S, Kalff JC, Weber O, Kirschning C, Coch C, Kalinke U, Wenzel J, Kurts C, Zawatzky R, Holzmann B, Layland L, Schultze JL, Burgdorf S, den Haan JM, Knolle PA, Limmer A (2012) Expression of type I interferon by splenic macrophages suppresses adaptive immunity during sepsis. EMBO J 31(1):201–213. doi: 10.1038/emboj.2011.380 PubMedCrossRefGoogle Scholar
  50. 50.
    Mattei F, Schiavoni G, Tough DF (2010) Regulation of immune cell homeostasis by type I interferons. Cytokine & growth factor reviews 21(4):227–236. doi: 10.1016/j.cytogfr.2010.05.002 CrossRefGoogle Scholar
  51. 51.
    Garcia Z, Lemaitre F, van Rooijen N, Albert ML, Levy Y, Schwartz O, Bousso P (2012) Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph borne viral particles. Blood. doi: 10.1182/blood-2012-02-408179 Google Scholar
  52. 52.
    Ito S, Naito M, Kobayashi Y, Takatsuka H, Jiang S, Usuda H, Umezu H, Hasegawa G, Arakawa M, Shultz LD, Elomaa O, Tryggvason K (1999) Roles of a macrophage receptor with collagenous structure (MARCO) in host defense and heterogeneity of splenic marginal zone macrophages. Arch Histol Cytol 62(1):83–95PubMedCrossRefGoogle Scholar
  53. 53.
    Takahashi K, Umeda S, Shultz LD, Hayashi S, Nishikawa S (1994) Effects of macrophage colony-stimulating factor (M-CSF) on the development, differentiation, and maturation of marginal metallophilic macrophages and marginal zone macrophages in the spleen of osteopetrosis (op) mutant mice lacking functional M-CSF activity. J Leukoc Biol 55(5):581–588PubMedGoogle Scholar
  54. 54.
    Kang YS, Kim JY, Bruening SA, Pack M, Charalambous A, Pritsker A, Moran TM, Loeffler JM, Steinman RM, Park CG (2004) The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of Streptococcus pneumoniae in the marginal zone of mouse spleen. Proc Natl Acad Sci U S A 101(1):215–220. doi: 10.1073/pnas.0307124101 PubMedCrossRefGoogle Scholar
  55. 55.
    Kang YS, Yamazaki S, Iyoda T, Pack M, Bruening SA, Kim JY, Takahara K, Inaba K, Steinman RM, Park CG (2003) SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran. Int Immunol 15(2):177–186PubMedCrossRefGoogle Scholar
  56. 56.
    Geijtenbeek TB, Groot PC, Nolte MA, van Vliet SJ, Gangaram-Panday ST, van Duijnhoven GC, Kraal G, van Oosterhout AJ, van Kooyk Y (2002) Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo. Blood 100(8):2908–2916. doi: 10.1182/blood-2002-04-1044 PubMedCrossRefGoogle Scholar
  57. 57.
    Nolte MA, Arens R, Kraus M, van Oers MH, Kraal G, van Lier RA, Mebius RE (2004) B cells are crucial for both development and maintenance of the splenic marginal zone. J Immunol 172(6):3620–3627PubMedGoogle Scholar
  58. 58.
    You Y, Myers RC, Freeberg L, Foote J, Kearney JF, Justement LB, Carter RH (2011) Marginal zone B cells regulate antigen capture by marginal zone macrophages. J Immunol 186(4):2172–2181. doi: 10.4049/jimmunol.1002106 PubMedCrossRefGoogle Scholar
  59. 59.
    You Y, Zhao H, Wang Y, Carter RH (2009) Cutting edge: primary and secondary effects of CD19 deficiency on cells of the marginal zone. J Immunol 182(12):7343–7347. doi: 10.4049/jimmunol.0804295 PubMedCrossRefGoogle Scholar
  60. 60.
    Kang YS, Do Y, Lee HK, Park SH, Cheong C, Lynch RM, Loeffler JM, Steinman RM, Park CG (2006) A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Cell 125(1):47–58. doi: 10.1016/j.cell.2006.01.046 PubMedCrossRefGoogle Scholar
  61. 61.
    Koppel EA, Wieland CW, van den Berg VC, Litjens M, Florquin S, van Kooyk Y, van der Poll T, Geijtenbeek TB (2005) Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcus pneumoniae infection. Eur J Immunol 35(10):2962–2969. doi: 10.1002/eji.200526216 PubMedCrossRefGoogle Scholar
  62. 62.
    Miyake Y, Asano K, Kaise H, Uemura M, Nakayama M, Tanaka M (2007) Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. J Clin Invest 117(8):2268–2278. doi: 10.1172/JCI31990 PubMedCrossRefGoogle Scholar
  63. 63.
    McGaha TL, Chen Y, Ravishankar B, van Rooijen N, Karlsson MC (2011) Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood 117(20):5403–5412. doi: 10.1182/blood-2010-11-320028 PubMedCrossRefGoogle Scholar
  64. 64.
    Mizui M, Shikina T, Arase H, Suzuki K, Yasui T, Rennert PD, Kumanogoh A, Kikutani H (2008) Bimodal regulation of T cell-mediated immune responses by TIM-4. Int Immunol 20(5):695–708PubMedCrossRefGoogle Scholar
  65. 65.
    Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH (2010) TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 235(1):172–189Google Scholar
  66. 66.
    Wermeling F, Chen Y, Pikkarainen T, Scheynius A, Winqvist O, Izui S, Ravetch JV, Tryggvason K, Karlsson MC (2007) Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus. The Journal of experimental medicine 204(10):2259–2265. doi: 10.1084/jem.20070600 PubMedCrossRefGoogle Scholar
  67. 67.
    Ravishankar B, Liu H, Shinde R, Chandler P, Baban B, Tanaka M, Munn DH, Mellor AL, Karlsson MC, McGaha TL (2012) Tolerance to apoptotic cells is regulated by indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A 109(10):3909–3914. doi: 10.1073/pnas.1117736109 PubMedCrossRefGoogle Scholar
  68. 68.
    Anthony RM, Wermeling F, Ravetch JV (2012) Novel roles for the IgG Fc glycan. Ann N Y Acad Sci 1253:170–180. doi: 10.1111/j.1749-6632.2011.06305.x PubMedCrossRefGoogle Scholar
  69. 69.
    Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci U S A 105(50):19571–19578. doi: 10.1073/pnas.0810163105 PubMedCrossRefGoogle Scholar
  70. 70.
    Anthony RM, Kobayashi T, Wermeling F, Ravetch JV (2011) Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 475(7354):110–113. doi: 10.1038/nature10134 PubMedCrossRefGoogle Scholar
  71. 71.
    Kranich J, Krautler NJ, Heinen E, Polymenidou M, Bridel C, Schildknecht A, Huber C, Kosco-Vilbois MH, Zinkernagel R, Miele G, Aguzzi A (2008) Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8. The Journal of experimental medicine 205(6):1293–1302. doi: 10.1084/jem.20071019 PubMedCrossRefGoogle Scholar
  72. 72.
    Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M, Uchiyama Y, Nagata S (2004) Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304(5674):1147–1150PubMedCrossRefGoogle Scholar
  73. 73.
    Shao WH, Zhen Y, Eisenberg RA, Cohen PL (2009) The Mer receptor tyrosine kinase is expressed on discrete macrophage subpopulations and mainly uses Gas6 as its ligand for uptake of apoptotic cells. Clin Immunol 133(1):138–144PubMedCrossRefGoogle Scholar
  74. 74.
    Rahman ZS, Shao WH, Khan TN, Zhen Y, Cohen PL (2010) Impaired apoptotic cell clearance in the germinal center by Mer-deficient tingible body macrophages leads to enhanced antibody-forming cell and germinal center responses. J Immunol 185(10):5859–5868Google Scholar
  75. 75.
    Smith JP, Burton GF, Tew JG, Szakal AK (1998) Tingible body macrophages in regulation of germinal center reactions. Dev Immunol 6(3–4):285–294PubMedCrossRefGoogle Scholar
  76. 76.
    Martinez-Pomares L, Hanitsch LG, Stillion R, Keshav S, Gordon S (2005) Expression of mannose receptor and ligands for its cysteine-rich domain in venous sinuses of human spleen. Lab Invest 85(10):1238–1249PubMedCrossRefGoogle Scholar
  77. 77.
    Martens JH, Kzhyshkowska J, Falkowski-Hansen M, Schledzewski K, Gratchev A, Mansmann U, Schmuttermaier C, Dippel E, Koenen W, Riedel F, Sankala M, Tryggvason K, Kobzik L, Moldenhauer G, Arnold B, Goerdt S (2006) Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis. J Pathol 208(4):574–589. doi: 10.1002/path.1921 PubMedCrossRefGoogle Scholar
  78. 78.
    Steiniger B, Timphus EM, Barth PJ (2006) The splenic marginal zone in humans and rodents: an enigmatic compartment and its inhabitants. Histochemistry and cell biology 126(6):641–648. doi: 10.1007/s00418-006-0210-5 PubMedCrossRefGoogle Scholar
  79. 79.
    Pack M, Trumpfheller C, Thomas D, Park CG, Granelli-Piperno A, Munz C, Steinman RM (2008) DEC-205/CD205+ dendritic cells are abundant in the white pulp of the human spleen, including the border region between the red and white pulp. Immunology 123(3):438–446. doi: 10.1111/j.1365-2567.2007.02710.x PubMedCrossRefGoogle Scholar
  80. 80.
    Lammermann T, Sixt M (2008) The microanatomy of T-cell responses. Immunol Rev 221:26–43. doi: 10.1111/j.1600-065X.2008.00592.x PubMedCrossRefGoogle Scholar
  81. 81.
    Gray EE, Cyster JG (2012) Lymph node macrophages. Journal of innate immunity 4(5–6):424–436. doi: 10.1159/000337007 PubMedCrossRefGoogle Scholar
  82. 82.
    Gretz JE, Norbury CC, Anderson AO, Proudfoot AE, Shaw S (2000) Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. The Journal of experimental medicine 192(10):1425–1440PubMedCrossRefGoogle Scholar
  83. 83.
    Nolte MA, Belien JA, Schadee-Eestermans I, Jansen W, Unger WW, van Rooijen N, Kraal G, Mebius RE (2003) A conduit system distributes chemokines and small blood-borne molecules through the splenic white pulp. The Journal of experimental medicine 198(3):505–512. doi: 10.1084/jem.20021801 PubMedCrossRefGoogle Scholar
  84. 84.
    Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, Pabst R, Lutz MB, Sorokin L (2005) The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22(1):19–29. doi: 10.1016/j.immuni.2004.11.013 PubMedCrossRefGoogle Scholar
  85. 85.
    Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A, Mebius RE, von Andrian UH, Carroll MC (2009) Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30(2):264–276. doi: 10.1016/j.immuni.2008.12.014 PubMedCrossRefGoogle Scholar
  86. 86.
    Bajenoff M, Germain RN (2009) B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells. Blood 114(24):4989–4997. doi: 10.1182/blood-2009-06-229567 PubMedCrossRefGoogle Scholar
  87. 87.
    Barral P, Polzella P, Bruckbauer A, van Rooijen N, Besra GS, Cerundolo V, Batista FD (2010) CD169(+) macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes. Nat Immunol 11(4):303–312. doi: 10.1038/ni.1853 PubMedCrossRefGoogle Scholar
  88. 88.
    Chtanova T, Han SJ, Schaeffer M, van Dooren GG, Herzmark P, Striepen B, Robey EA (2009) Dynamics of T cell, antigen-presenting cell, and pathogen interactions during recall responses in the lymph node. Immunity 31(2):342–355. doi: 10.1016/j.immuni.2009.06.023 PubMedCrossRefGoogle Scholar
  89. 89.
    Coombes JL, Han SJ, van Rooijen N, Raulet DH, Robey EA (2012) Infection-induced regulation of natural killer cells by macrophages and collagen at the lymph node subcapsular sinus. Cell reports 2(1):124–135. doi: 10.1016/j.celrep.2012.06.001 PubMedCrossRefGoogle Scholar
  90. 90.
    Kastenmuller W, Torabi-Parizi P, Subramanian N, Lammermann T, Germain RN (2012) A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell 150(6):1235–1248. doi: 10.1016/j.cell.2012.07.021 PubMedCrossRefGoogle Scholar
  91. 91.
    Moseman EA, Iannacone M, Bosurgi L, Tonti E, Chevrier N, Tumanov A, Fu YX, Hacohen N, von Andrian UH (2012) B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity. Immunity 36(3):415–426. doi: 10.1016/j.immuni.2012.01.013 PubMedCrossRefGoogle Scholar
  92. 92.
    Yu P, Wang Y, Chin RK, Martinez-Pomares L, Gordon S, Kosco-Vibois MH, Cyster J, Fu YX (2002) B cells control the migration of a subset of dendritic cells into B cell follicles via CXC chemokine ligand 13 in a lymphotoxin-dependent fashion. J Immunol 168(10):5117–5123PubMedGoogle Scholar
  93. 93.
    Gray EE, Friend S, Suzuki K, Phan TG, Cyster JG (2012) Subcapsular sinus macrophage fragmentation and CD169+ bleb acquisition by closely associated IL-17-committed innate-like lymphocytes. PLoS One 7(6):e38258. doi: 10.1371/journal.pone.0038258 PubMedCrossRefGoogle Scholar
  94. 94.
    Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Kim YA, Cloninger MJ, Martinez-Pomares L, Gordon S, Turley SJ, Carroll MC (2010) Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol 11(5):427–434Google Scholar
  95. 95.
    Albacker LA, Yu S, Bedoret D, Lee WL, Umetsu SE, Monahan S, Freeman GJ, Umetsu DT, Dekruyff RH (2012) TIM-4, expressed by medullary macrophages, regulates respiratory tolerance by mediating phagocytosis of antigen-specific T cells. Mucosal immunology. doi: 10.1038/mi.2012.100 PubMedGoogle Scholar
  96. 96.
    Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A, Tomura M, Kanagawa O, Fujii S, Tanaka M (2011) CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 34(1):85–95. doi: 10.1016/j.immuni.2010.12.011 PubMedCrossRefGoogle Scholar
  97. 97.
    Angel CE, Chen CJ, Horlacher OC, Winkler S, John T, Browning J, MacGregor D, Cebon J, Dunbar PR (2009) Distinctive localization of antigen-presenting cells in human lymph nodes. Blood 113(6):1257–1267. doi: 10.1182/blood-2008-06-165266 PubMedCrossRefGoogle Scholar
  98. 98.
    Cerutti A, Rescigno M (2008) The biology of intestinal immunoglobulin A responses. Immunity 28(6):740–750. doi: 10.1016/j.immuni.2008.05.001 PubMedCrossRefGoogle Scholar
  99. 99.
    Bhogal HS, Kennedy LJ, Babic K, Reynolds JD (2004) The role of macrophages in the removal of apoptotic B-cells in the sheep ileal Peyer’s patch. Dev Comp Immunol 28(7–8):843–853. doi: 10.1016/j.dci.2003.12.006 PubMedCrossRefGoogle Scholar
  100. 100.
    Hume DA, Gordon S (1983) Mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Identification of resident macrophages in renal medullary and cortical interstitium and the juxtaglomerular complex. J Exp Med 157(5):1704–1709PubMedCrossRefGoogle Scholar
  101. 101.
    Witmer-Pack MD, Hughes DA, Schuler G, Lawson L, McWilliam A, Inaba K, Steinman RM, Gordon S (1993) Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J Cell Sci 104(Pt 4):1021–1029PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Molecular Cell Biology and ImmunologyVU University Medical CenterAmsterdamthe Netherlands
  2. 2.School of Molecular Medical SciencesUniversity of Nottingham, Queen’s Medical CentreNottinghamUK

Personalised recommendations