Review Article | Published:

Tissue-resident macrophages

Nature Immunology volume 14, pages 986995 (2013) | Download Citation

Abstract

Tissue-resident macrophages are a heterogeneous population of immune cells that fulfill tissue-specific and niche-specific functions. These range from dedicated homeostatic functions, such as clearance of cellular debris and iron processing, to central roles in tissue immune surveillance, response to infection and the resolution of inflammation. Recent studies highlight marked heterogeneity in the origins of tissue macrophages that arise from hematopoietic versus self-renewing embryo-derived populations. We discuss the tissue niche-specific factors that dictate cell phenotype, the definition of which will allow new strategies to promote the restoration of tissue homeostasis. Understanding the mechanisms that dictate tissue macrophage heterogeneity should explain why simplified models of macrophage activation do not explain the extent of heterogeneity seen in vivo.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Leçons sur la pathologie comparée de l'inflammation (Masson, 1892).

  2. 2.

    Das reticuloendotheliale system. Erg. Inn. Med. Kinderheilk 26, 1–117 (1924).

  3. 3.

    , & Discrimination of two types of phagocytic cells in the connective tissues by the supravital technique. Contrib. Embryol. (Am) 16, 125–162 (1925).

  4. 4.

    & The fine structure and peroxidase activity of resident and exudate peritoneal macrophages in the guinea pig. The Reticuloendothelial System and Immune Phenomena: Advances in Experimental Medicine and Biology (eds., N. Di Luzio & K. Flemming) 15, 19–31 (1971).

  5. 5.

    & The origin and kinetics of mononuclear phagocytes. J. Exp. Med. 128, 415–435 (1968).

  6. 6.

    et al. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ. 46, 845–852 (1972).

  7. 7.

    & Origin and kinetics of resident tissue macrophages. Parabiosis studies with radiolabelled leucocytes. Cell Tissue Kinet. 17, 25–39 (1984).

  8. 8.

    , & Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89. Lab. Invest. 46, 165–170 (1982).

  9. 9.

    & Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J. Invest. Dermatol. 88, 17–20 (1987).

  10. 10.

    , , & Maintenance of peritoneal macrophages in the steady state. J. Leukoc. Biol. 44, 367–375 (1988).

  11. 11.

    et al. Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages. J. Leukoc. Biol. 59, 133–138 (1996).

  12. 12.

    Development and differentiation of macrophages and related cells: historical review and current concepts. J. Clin. Exp. Hematop. 41, 1–31 (2000).

  13. 13.

    & Origins and functions of phagocytes in the embryo. Exp. Hematol. 28, 601–611 (2000).

  14. 14.

    et al. Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J. Exp. Med. 206, 3089–3100 (2009).

  15. 15.

    et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010).This study demonstrates the early embryonic origins of adult microglia, which are maintained throughout life by local self renewal.

  16. 16.

    et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209, 1167–1181 (2012).

  17. 17.

    et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336, 86–90 (2012).This work is a demonstration of the clear potential for widespread tissue seeding of macrophages from the yolk sac.

  18. 18.

    et al. Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Immunity 37, 1050–1060 (2012).

  19. 19.

    et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13, 753–760 (2012).Studies in refs. 18 and 19 describe an important tissue-specific role for IL-34 in the development and maintenance of Langerhans cells and microglia.

  20. 20.

    , , & Re(de)fining the dendritic cell lineage. Nat. Immunol. 13, 1145–1154 (2012).

  21. 21.

    et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).

  22. 22.

    et al. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol. 6, 498–510 (2013).

  23. 23.

    , & Turnover of epidermal Langerhans' cells. N. Engl. J. Med. 351, 2661–2662 (2004).

  24. 24.

    et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3, 1135–1141 (2002).

  25. 25.

    , , , & Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10, 1538–1543 (2007).This work is a demonstration of the autonomy of adult microglia from potential peripheral progenitors.

  26. 26.

    et al. Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat. Neurosci. 10, 1544–1553 (2007).

  27. 27.

    et al. Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc. Natl. Acad. Sci. USA 109, 15018–15023 (2012).

  28. 28.

    et al. A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. Eur. J. Immunol. 41, 2155–2164 (2011).This is the first demonstration that tissue-resident macrophages in vascular tissues can renew by local proliferation without substantial monocytic input.

  29. 29.

    et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38, 792–804 (2013).This work demonstrates the clear potential for widespread tissue seeding of macrophages from the yolk sac.

  30. 30.

    , & Distinct differentiation potential of blood monocyte subsets in the lung. J. Immunol. 178, 2000–2007 (2007).

  31. 31.

    et al. Origin of monocytes and macrophages in a committed progenitor. Nat. Immunol. 14, 821–830 (2013).

  32. 32.

    et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13, 1118–1128 (2012).

  33. 33.

    et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345, 442–444 (1990).

  34. 34.

    Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol. 8, 533–544 (2008).

  35. 35.

    Trophic macrophages in development and disease. Nat. Rev. Immunol. 9, 259–270 (2009).

  36. 36.

    et al. Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis. Blood 98, 74–84 (2001).

  37. 37.

    et al. The mechanism of shared but distinct CSF-1R signaling by the non-homologous cytokines IL-34 and CSF-1. Biochim. Biophys. Acta 1824, 938–945 (2012).

  38. 38.

    et al. IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation. Cell Death Differ. 17, 1917–1927 (2010).

  39. 39.

    & Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood 119, 1810–1820 (2012).

  40. 40.

    et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332, 1284–1288 (2011).This work demonstrates that parasite infection expands tissue-resident macrophages in an IL-4–dependent manner without the need for monocyte recruitment.

  41. 41.

    et al. Distinct bone marrow-derived and tissue resident macrophage-lineages proliferate at key stages during inflammation. Nat. Commun. 4, 1886 (2013).This work definitively demonstrates that peripherally derived inflammatory macrophages proliferate during inflammation.

  42. 42.

    , & Macrophage polarization comes of age. Immunity 23, 344–346 (2005).

  43. 43.

    , , , & Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229, 176–185 (2013).

  44. 44.

    & Alternative activation of macrophages: mechanism and functions. Immunity 32, 593–604 (2010).

  45. 45.

    et al. Latent enhancers activated by stimulation in differentiated cells. Cell 152, 157–171 (2013).

  46. 46.

    et al. Macrophage receptors and immune recognition. Annu. Rev. Immunol. 23, 901–944 (2005).

  47. 47.

    , & Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2, 675–680 (2001).

  48. 48.

    & NODs: intracellular proteins involved in inflammation and apoptosis. Nat. Rev. Immunol. 3, 371–382 (2003).

  49. 49.

    et al. Conditional macrophage ablation demonstrates that resident macrophages initiate acute peritoneal inflammation. J. Immunol. 174, 2336–2342 (2005).

  50. 50.

    et al. Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice. Am. J. Physiol. Lung Cell Mol. Physiol. 282, L1245–L1252 (2002).

  51. 51.

    et al. Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. J. Immunol. 162, 1685–1691 (1999).

  52. 52.

    et al. The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell programming and the progression of phagocytosis. J. Immunol. 181, 3549–3557 (2008).

  53. 53.

    et al. Resident peritoneal macrophages and mast cells are important cellular sites of COX-1 and COX-2 activity during acute peritoneal inflammation. Arch. Immunol. Ther. Exp. (Warsz.) 57, 459–466 (2009).

  54. 54.

    et al. Resident peritoneal leukocytes are important sources of MMP-9 during zymosan peritonitis: superior contribution of macrophages over mast cells. Immunol. Lett. 113, 99–106 (2007).

  55. 55.

    , , & Review of the macrophage disappearance reaction. J. Leukoc. Biol. 57, 361–367 (1995).

  56. 56.

    , , , & The myeloid 7/4-antigen defines recently generated inflammatory macrophages and is synonymous with Ly-6B. J. Leukoc. Biol. 88, 169–180 (2010).

  57. 57.

    et al. Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation. J. Exp. Med. 196, 1515–1521 (2002).

  58. 58.

    et al. Paracetamol reduces influenza-induced immunopathology in a mouse model of infection without compromising virus clearance or the generation of protective immunity. Thorax 66, 368–374 (2011).

  59. 59.

    , & Alveolar macrophages transport pathogens to lung draining lymph nodes. J. Immunol. 183, 1983–1989 (2009).

  60. 60.

    , , , & Modulation of dendritic cell trafficking to and from the airways. J. Immunol. 176, 3578–3584 (2006).

  61. 61.

    et al. Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. Am. J. Respir. Crit. Care Med. 184, 547–560 (2011).

  62. 62.

    & Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens. PLoS Pathog. 7, e1002003 (2011).

  63. 63.

    , , , & Macrophage heterogeneity and acute inflammation. Eur. J. Immunol. 41, 2503–2508 (2011).

  64. 64.

    , , , & Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci. 14, 1142–1149 (2011).

  65. 65.

    et al. Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J. Exp. Med. 209, 123–137 (2012).

  66. 66.

    , , & A specific role of integrin Mac-1 in accelerated macrophage efflux to the lymphatics. Blood 106, 3234–3241 (2005).

  67. 67.

    , , , & Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis. Nephrol. Dial. Transplant. 16, 1638–1647 (2001).

  68. 68.

    et al. Local macrophage proliferation in human glomerulonephritis. Kidney Int. 54, 143–151 (1998).

  69. 69.

    et al. Source and characterization of hepatic macrophages in acetaminophen-induced acute liver failure in humans. Hepatology 56, 735–746 (2012).

  70. 70.

    et al. Differential roles of macrophages in diverse phases of skin repair. J. Immunol. 184, 3964–3977 (2010).

  71. 71.

    et al. Systemic analysis of PPARgamma in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity. J. Immunol. 189, 2614–2624 (2012).

  72. 72.

    , , & Host responses in tissue repair and fibrosis. Annu. Rev. Pathol. 8, 241–276 (2013).

  73. 73.

    et al. Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. Cell 153, 376–388 (2013).

  74. 74.

    & Apoptotic cell removal in development and tissue homeostasis. Trends Immunol. 27, 244–250 (2006).

  75. 75.

    , & Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front Cell Neurosci 7, 34 (2013).

  76. 76.

    et al. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity 38, 555–569 (2013).

  77. 77.

    & Clearance of apoptotic cells by phagocytes. Cell Death Differ. 15, 243–250 (2008).

  78. 78.

    , & The role of complement in the development of systemic lupus erythematosus. Annu. Rev. Immunol. 22, 431–456 (2004).

  79. 79.

    et al. 12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. Immunity 36, 834–846 (2012).This work demonstrates that tissue-resident macrophages can actively divert apoptotic cell clearance to themselves rather than recruited inflammatory monocyte-derived cells.

  80. 80.

    et al. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304, 1147–1150 (2004).

  81. 81.

    et al. TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27, 927–940 (2007).

  82. 82.

    et al. Identification of Tim4 as a phosphatidylserine receptor. Nature 450, 435–439 (2007).

  83. 83.

    , , , & Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J. Immunol. 178, 5635–5642 (2007).

  84. 84.

    et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411, 207–211 (2001).

  85. 85.

    et al. Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature 437, 754–758 (2005).

  86. 86.

    Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors. Immunol. Rev. 220, 237–250 (2007).

  87. 87.

    et al. CD169+ macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nat. Med. 19, 429–436 (2013).

  88. 88.

    et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science 292, 1546–1549 (2001).

  89. 89.

    , , , & Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. Nat. Immunol. 6, 49–56 (2005).

  90. 90.

    Macrophages and systemic iron homeostasis. J. Innate Immun. 4, 446–453 (2012).

  91. 91.

    et al. Identification of the haemoglobin scavenger receptor. Nature 409, 198–201 (2001).

  92. 92.

    et al. Identification of the receptor scavenging hemopexin-heme complexes. Blood 106, 2572–2579 (2005).

  93. 93.

    et al. Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages. Nature 495, 524–528 (2013).

  94. 94.

    et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332, 243–247 (2011).

  95. 95.

    et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447, 1116–1120 (2007).

  96. 96.

    et al. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab. 7, 485–495 (2008).

  97. 97.

    et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 7, 496–507 (2008).

  98. 98.

    et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480, 104–108 (2011).This is an interesting demonstration of the importance of alternatively activated macrophages in the physiological response to cold.

  99. 99.

    Germinal centers. Annu. Rev. Immunol. 12, 117–139 (1994).

  100. 100.

    & Structure and function of the spleen. Nat. Rev. Immunol. 5, 606–616 (2005).

  101. 101.

    & Innate immune functions of macrophage subpopulations in the spleen. J. Innate Immun. 4, 437–445 (2012).

  102. 102.

    et al. Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457, 318–321 (2009).This is a demonstration of the restriction of Spi-C expression to red pulp macrophages and its selective importance for their red pulp macrophage development and hence for splenic iron homeostasis.

  103. 103.

    et al. Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo. Blood 100, 2908–2916 (2002).

  104. 104.

    et al. Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell 80, 603–609 (1995).

  105. 105.

    et al. 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. USA 101, 215–220 (2004).

  106. 106.

    et al. SIGN-R1 contributes to protection against lethal pneumococcal infection in mice. J. Exp. Med. 200, 1383–1393 (2004).

  107. 107.

    et al. Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone. J. Exp. Med. 198, 333–340 (2003).

  108. 108.

    et al. The nuclear receptor LXRα controls the functional specialization of splenic macrophages. Nat. Immunol. 14, 831–839 (2013).

  109. 109.

    & Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-alpha/beta producers in mice upon intravenous challenge with herpes simplex virus. Scand. J. Immunol. 49, 391–394 (1999).

  110. 110.

    et al. Sialoadhesin promotes rapid proinflammatory and type I IFN responses to a sialylated pathogen, Campylobacter jejuni. J. Immunol. 189, 2414–2422 (2012).

  111. 111.

    et al. Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nat. Immunol. 13, 51–57 (2012).This paper describes an interesting selective role for splenic metallophilic macrophages as a potential infectious viral reservoir that drives adaptive immunity.

  112. 112.

    et al. Effective collaboration between marginal metallophilic macrophages and CD8+ dendritic cells in the generation of cytotoxic T cells. Proc. Natl. Acad. Sci. USA 107, 216–221 (2010).

  113. 113.

    , , & Prolonged apoptotic cell accumulation in germinal centers of Mer-deficient mice causes elevated B cell and CD4+ Th cell responses leading to autoantibody production. J. Immunol. 190, 1433–1446 (2013).

  114. 114.

    et al. Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153, 362–375 (2013).

  115. 115.

    et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J. Exp. Med. 208, 261–271 (2011).

  116. 116.

    et al. Calcitonin receptor antibodies in the identification of osteoclasts. Bone 25, 1–8 (1999).

  117. 117.

    & Role of the macrophage in erythropoiesis. Pathol. Int. 49, 841–848 (1999).

  118. 118.

    et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456–1458 (2011).

  119. 119.

    , , & Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat. Neurosci. 14, 1227–1235 (2011).

  120. 120.

    & Intestinal macrophages: well educated exceptions from the rule. Trends Immunol. 34, 162–168 (2013).

  121. 121.

    et al. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood 110, 4077–4085 (2007).

  122. 122.

    , & Dendritic cell and macrophage heterogeneity in vivo. Immunity 35, 323–335 (2011).

  123. 123.

    & The molecular basis of pulmonary alveolar proteinosis. Clin. Immunol. 135, 223–235 (2010).

  124. 124.

    , , , & The prolonged life-span of alveolar macrophages. Am. J. Respir. Cell Mol. Biol. 38, 380–385 (2008).

  125. 125.

    et al. Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. J. Clin. Invest. 119, 3723–3738 (2009).

  126. 126.

    et al. The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J. Immunol. 169, 3876–3882 (2002).

  127. 127.

    et al. 12/15-Lipoxygenase regulates the inflammatory response to bacterial products in vivo. J. Immunol. 181, 6514–6524 (2008).

  128. 128.

    et al. Resident pleural macrophages are key orchestrators of neutrophil recruitment in pleural inflammation. Am. J. Respir. Crit. Care Med. 173, 540–547 (2006).

  129. 129.

    & Development and homeostasis of 'resident' myeloid cells: the case of the Langerhans cell. Trends Immunol. 31, 438–445 (2010).

  130. 130.

    , & Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8, 935–947 (2008).

  131. 131.

    et al. The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling. J. Leukoc. Biol. 80, 838–849 (2006).

  132. 132.

    et al. Dectin-2 is predominantly myeloid restricted and exhibits unique activation-dependent expression on maturing inflammatory monocytes elicited in vivo. Eur. J. Immunol. 35, 2163–2174 (2005).

  133. 133.

    et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nat. Immunol. 4, 380–386 (2003).

  134. 134.

    et al. Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. EMBO J. 23, 969–979 (2004).

Download references

Acknowledgements

This work was supported by funding from the Medical Research Council (MRC), including Senior Fellowship and Project grants to P.R.T. (G0601617/1, MR/J002151/1 and MR/K02003X/1) and a Programme grant to J.E.A. (MR/K01207X/1). P.R.T. is additionally supported through a Wellcome Trust Institutional Strategic Support Fund (097824/Z/11). L.C.D. is an MRC-funded PhD student and holds a Cardiff University 125 for 125 Scholarship. S.J.J. is funded by a University of Edinburgh Chancellor's Fellowship.

Author information

Affiliations

  1. Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.

    • Luke C Davies
    •  & Philip R Taylor
  2. Medical Research Council Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.

    • Stephen J Jenkins
  3. Centre for Immunity, Infection and Evolution, and the Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

    • Judith E Allen

Authors

  1. Search for Luke C Davies in:

  2. Search for Stephen J Jenkins in:

  3. Search for Judith E Allen in:

  4. Search for Philip R Taylor in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Philip R Taylor.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ni.2705

Further reading