Skip to main content
SpringerLink
Log in

Monocyte and macrophage heterogeneity and Toll-like receptors in the lung

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Mononuclear phagocytes are crucial components of the innate host defense system. Cells such as macrophages and monocytes phagocytose and process pathogens, produce inflammatory mediators, and link the innate and the adaptive immune systems. The role of innate immune receptors such as Toll-like receptors (TLRs) in the recognition of pathogens is critical for mounting a precise and targeted immune response. This review focuses attention on the development of monocytes and macrophages, various populations of macrophages, and the expression and function of TLRs on macrophages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Aharonson-Raz K, Singh B (2010) Pulmonary intravascular macrophages and endotoxin-induced pulmonary pathophysiology in horses. Can J Vet Res 74:45–49

    CAS  PubMed  Google Scholar 

  • Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680

    CAS  PubMed  Google Scholar 

  • Alvarez B, Revilla C, Domenech N, Perez C, Martinez P, Alonso F, Ezquerra A, Domiguez J (2008) Expression of toll-like receptor 2 (TLR2) in porcine leukocyte subsets and tissues. Vet Res 39:13

    PubMed  Google Scholar 

  • An H, Xu H, Yu Y, Zhang M, Qi R, Yan X, Liu S, Wang W, Guo Z, Qin Z, Cao X (2002) Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways. Immunol Lett 81:165–169

    CAS  PubMed  Google Scholar 

  • Bedoret D, Wallemacq H, Marichal T, Desmet C, Quesada Calvo F, Henry E, Closset R, Dewals B, Thielen C, Gustin P, Leval L de, Van Rooijen N, Le Moine A, Vanderplasschen A, Cataldo D, Drion PV, Moser M, Lekeux P, Bureau F (2009) Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. J Clin Invest 119:3723–3738

    CAS  PubMed  Google Scholar 

  • Bessa J, Jegerlehner A, Hinton HJ, Pumpens P, Saudan P, Schneider P, Bachmann MF (2009) Alveolar macrophages and lung dendritic cells sense RNA and drive mucosal IgA responses. J Immunol 183:3788–3799

    CAS  PubMed  Google Scholar 

  • Blander JM, Medzhitov R (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304:1014–1018

    CAS  PubMed  Google Scholar 

  • Bonfield TL, Konstan MW, Burfeind P, Panuska JR, Hilliard JB, Berger M (1995) Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. Am J Respir Cell Mol Biol 13:257–261

    CAS  PubMed  Google Scholar 

  • Bouteiller O de, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE, Caux C (2005) Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem 280:38133–38145

    PubMed  Google Scholar 

  • Bowden DH (1984) The alveolar macrophage. Environ Health Perspect 55:327–341

    CAS  PubMed  Google Scholar 

  • Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285:732–736

    CAS  PubMed  Google Scholar 

  • Brown V, Brown RA, Ozinsky A, Hesselberth JR, Fields S (2006) Binding specificity of Toll-like receptor cytoplasmic domains. Eur J Immunol 36:742–753

    CAS  PubMed  Google Scholar 

  • Cabanski M, Steinmuller M, Marsh LM, Surdziel E, Seeger W, Lohmeyer J (2008) PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages. Am J Respir Cell Mol Biol 38:26–31

    CAS  PubMed  Google Scholar 

  • Chang JS, Russell GC, Jann O, Glass EJ, Werling D, Haig DM (2009) Molecular cloning and characterization of Toll-like receptors 1-10 in sheep. Vet Immunol Immunopathol 127:94–105

    CAS  PubMed  Google Scholar 

  • Chang S, Dolganiuc A, Szabo G (2007) Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins. J Leukoc Biol 82:479–487

    CAS  PubMed  Google Scholar 

  • Chaung HC, Chen CW, Hsieh BL, Chung WB (2010) Toll-like receptor expressions in porcine alveolar macrophages and dendritic cells in responding to poly IC stimulation and porcine reproductive and respiratory syndrome virus (PRRSV) infection. Comp Immunol Microbiol Infect Dis 33:197–213

    PubMed  Google Scholar 

  • Choe KM, Werner T, Stoven S, Hultmark D, Anderson KV (2002) Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science 296:359–362

    CAS  PubMed  Google Scholar 

  • Crabtree TD, Jin L, Raymond DP, Pelletier SJ, Houlgrave CW, Gleason TG, Pruett TL, Sawyer RG (2001) Preexposure of murine macrophages to CpG oligonucleotide results in a biphasic tumor necrosis factor alpha response to subsequent lipopolysaccharide challenge. Infect Immun 69:2123–2129

    CAS  PubMed  Google Scholar 

  • De Nardo D, De Nardo CM, Nguyen T, Hamilton JA, Scholz GM (2009) Signaling crosstalk during sequential TLR4 and TLR9 activation amplifies the inflammatory response of mouse macrophages. J Immunol 183:8110–8118

    PubMed  Google Scholar 

  • Demedts IK, Bracke KR, Maes T, Joos GF, Brusselle GG (2006) Different roles for human lung dendritic cell subsets in pulmonary immune defense mechanisms. Am J Respir Cell Mol Biol 35:387–393

    CAS  PubMed  Google Scholar 

  • Dempsey PW, Vaidya SA, Cheng G (2003) The art of war: innate and adaptive immune responses. Cell Mol Life Sci 60:2604–2621

    CAS  PubMed  Google Scholar 

  • Diebold SS, Kaisho T, Hemmi H, Akira S, Reise Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529

    CAS  PubMed  Google Scholar 

  • Doyle S, Vaidya S, O'Connell R, Dadgostar H, Dempsey P, Wu T, Rao G, Sun R, Haberland M, Modlin R, Cheng G (2002) IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17:251–263

    CAS  PubMed  Google Scholar 

  • Droemann D, Goldmann T, Tiedje T, Zabel P, Dalhoff K, Schaaf B (2005) Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respir Res 6:68

    PubMed  Google Scholar 

  • Ewaschuk JB, Backer JL, Churchill TA, Obermeier F, Krause DO, Madsen KL (2007) Surface expression of Toll-like receptor 9 is upregulated on intestinal epithelial cells in response to pathogenic bacterial DNA. Infect Immun 75:2572–2579

    CAS  PubMed  Google Scholar 

  • Fernandez S, Jose P, Avdiushko MG, Kaplan AM, Cohen DA (2004) Inhibition of IL-10 receptor function in alveolar macrophages by Toll-like receptor agonists. J Immunol 172:2613–2620

    CAS  PubMed  Google Scholar 

  • Figueiredo MD, Vandenplas ML, Hurley DJ, Moore JN (2009) Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists. Vet Immunol Immunopathol 127:125–134

    CAS  PubMed  Google Scholar 

  • Flaminio MJ, Borges AS, Nydam DV, Horohov DW, Hecker R, Matychak MB (2007) The effect of CpG-ODN on antigen presenting cells of the foal. J Immune Based Ther Vaccines 5:1–17

    PubMed  Google Scholar 

  • Fulton SA, Reba SM, Pai RK, Pennini M, Torres M, Harding CV, Boom WH (2004) Inhibition of major histocompatibility complex II expression and antigen processing in murine alveolar macrophages by Mycobacterium bovis BCG and the 19-kilodalton mycobacterial lipoprotein. Infect Immun 72:2101–2110

    CAS  PubMed  Google Scholar 

  • Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82

    CAS  PubMed  Google Scholar 

  • Geissmann F, Gordon S, Hume DA, Mowat AM, Randolph GJ (2010a) Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol 10:453–460

    CAS  PubMed  Google Scholar 

  • Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K (2010b) Development of monocytes, macrophages, and dendritic cells. Science 327:656–661

    CAS  PubMed  Google Scholar 

  • Ghosh TK, Mickelson DJ, Solberg JC, Lipson KE, Inglefield JR, Alkan SS (2007) TLR-TLR cross talk in human PBMC resulting in synergistic and antagonistic regulation of type-1 and 2 interferons, IL-12 and TNF-alpha. Int Immunopharmacol 7:1111–1121

    CAS  PubMed  Google Scholar 

  • Gill SS, Suri SS, Janardhan KS, Caldwell S, Duke T, Singh B (2008) Role of pulmonary intravascular macrophages in endotoxin-induced lung inflammation and mortality in a rat model. Respir Res 9:69

    PubMed  Google Scholar 

  • Godleski JJ, Brain JD (1972) The origin of alveolar macrophages in mouse radiation chimeras. J Exp Med 136:630–643

    CAS  PubMed  Google Scholar 

  • Gorden KK, Qiu X, Battiste JJ, Wightman PP, Vasilakos JP, Alkan SS (2006a) Oligodeoxynucleotides differentially modulate activation of TLR7 and TLR8 by imidazoquinolines. J Immunol 177:8164–8170

    CAS  PubMed  Google Scholar 

  • Gorden KK, Qiu XX, Binsfeld CC, Vasilakos JP, Alkan SS (2006b) Cutting edge: activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides. J Immunol 177:6584–6587

    CAS  PubMed  Google Scholar 

  • Gordon S (2002) Pattern recognition receptors: doubling up for the innate immune response. Cell 111:927–930

    CAS  PubMed  Google Scholar 

  • Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964

    CAS  PubMed  Google Scholar 

  • Gould MP, Greene JA, Bhoj V, DeVecchio JL, Heinzel FP (2004) Distinct modulatory effects of LPS and CpG on IL-18-dependent IFN-gamma synthesis. J Immunol 172:1754–1762

    CAS  PubMed  Google Scholar 

  • Grage-Griebenow E, Zawatzky R, Kahlert H, Brade L, Flad H, Ernst M (2001) Identification of a novel dendritic cell-like subset of CD64(+)/CD16(+) blood monocytes. Eur J Immunol 31:48–56

    CAS  PubMed  Google Scholar 

  • Griebel PJ, Brownlie R, Manuja A, Nichani A, Mookherjee N, Popowych Y, Mutwiri G, Hecker R, Babiuk LA (2005) Bovine toll-like receptor 9: a comparative analysis of molecular structure, function and expression. Vet Immunol Immunopathol 108:11–16

    CAS  PubMed  Google Scholar 

  • Hajjar AM, O'Mahony DS, Ozinsky A, Underhill DM, Aderem A, Klebanoff SJ, Wilson CB (2001) Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. J Immunol 166:15–19

    CAS  PubMed  Google Scholar 

  • Hawn TR, Berrington WR, Smith IA, Uematsu S, Akira S, Aderem A, Smith KD, Skerrett SJ (2007) Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila. J Immunol 179:6981–6987

    CAS  PubMed  Google Scholar 

  • Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099–1103

    CAS  PubMed  Google Scholar 

  • Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526–1529

    CAS  PubMed  Google Scholar 

  • Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745

    CAS  PubMed  Google Scholar 

  • Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200

    CAS  PubMed  Google Scholar 

  • Henning LN, Azad AK, Parsa KV, Crowther JE, Tridandapani S, Schlesinger LS (2008) Pulmonary surfactant protein A regulates TLR expression and activity in human macrophages. J Immunol 180:7847–7858

    CAS  PubMed  Google Scholar 

  • Hirotani T, Lee PY, Kuwata H, Yamamoto M, Matsumoto M, Kawase I, Akira S, Takeda K (2005) The nuclear IkappaB protein IkappaBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria. J Immunol 174:3650–3657

    CAS  PubMed  Google Scholar 

  • Horng T, Barton GM, Flavell RA, Medzhitov R (2002) The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420:329–333

    CAS  PubMed  Google Scholar 

  • Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T, Endres S, Hartmann G (2002) Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 168:4531–4537

    CAS  PubMed  Google Scholar 

  • Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S (1999) Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752

    CAS  PubMed  Google Scholar 

  • Hume DA (2006) The mononuclear phagocyte system. Curr Opin Immunol 18:49–53

    CAS  PubMed  Google Scholar 

  • Hume DA (2008) Differentiation and heterogeneity in the mononuclear phagocyte system. Mucosal Immunol 1:432–441

    CAS  PubMed  Google Scholar 

  • Juarez E, Nunez C, Sada E, Ellner JJ, Schwander SK, Torres M (2010) Differential expression of Toll-like receptors on human alveolar macrophages and autologous peripheral monocytes. Respir Res 11:2

    PubMed  Google Scholar 

  • Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G, Bauer S (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol 3:499

    CAS  PubMed  Google Scholar 

  • Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ (2001) Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 194:863–869

    CAS  PubMed  Google Scholar 

  • Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S (2004) Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol 5:1061–1068

    CAS  PubMed  Google Scholar 

  • Kiemer AK, Senaratne RH, Hoppstadter J, Diesel B, Riley LW, Tabeta K, Bauer S, Beutler B, Zuraw BL (2008) Attenuated activation of macrophage TLR9 by DNA from virulent mycobacteria. J Innate Immun 1:29–45

    PubMed  Google Scholar 

  • Klinman DM (2004) Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 4:249–258

    CAS  PubMed  Google Scholar 

  • Kramer BW, Kallapur SG, Moss TJ, Nitsos I, Newnham JP, Jobe AH (2009) Intra-amniotic LPS modulation of TLR signaling in lung and blood monocytes of fetal sheep. Innate Immun 15:101–107

    CAS  PubMed  Google Scholar 

  • Krieg AM (2002) CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20:709–760

    CAS  PubMed  Google Scholar 

  • Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374:546–549

    CAS  PubMed  Google Scholar 

  • Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE, Graeber TG, Sieling PA, Liu YJ, Rea TH, Bloom BR, Modlin RL (2005) TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med 11:653–660

    CAS  PubMed  Google Scholar 

  • Kuramoto E, Yano O, Kimura Y, Baba M, Makino T, Yamamoto S, Yamamoto T, Kataoka T, Tokunaga T (1992) Oligonucleotide sequences required for natural killer cell activation. Jpn J Cancer Res 83:1128–1131

    CAS  PubMed  Google Scholar 

  • Leon B, Ardavin C (2008) Monocyte migration to inflamed skin and lymph nodes is differentially controlled by L-selectin and PSGL-1. Blood 111:3126–3130

    CAS  PubMed  Google Scholar 

  • Leon B, Martinez del Hoyo G, Parrillas V, Vargas HH, Sanchez-Mateos P, Longo N, Lopez-Bravo M, Ardavin C (2004) Dendritic cell differentiation potential of mouse monocytes: monocytes represent immediate precursors of CD8- and CD8+ splenic dendritic cells. Blood 103:2668–2676

    CAS  PubMed  Google Scholar 

  • Liu CF, Rivere M, Huang HJ, Puzo G, Wang JY (2010) Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression. Clin Exp Allergy 40:111–122

    CAS  PubMed  Google Scholar 

  • Lohmann-Matthes ML, Steinmuller C, Franke-Ullmann G (1994) Pulmonary macrophages. Eur Respir J 7:1678–1689

    CAS  PubMed  Google Scholar 

  • Lopez M, Sly LM, Luu Y, Young D, Cooper H, Reiner NE (2003) Mycobacterium tuberculosis protein induces macrophage apoptosis through toll-like receptor-2. J Immunol 170:2409–2416

    CAS  PubMed  Google Scholar 

  • Maris NA, Dessing MC, Vos AF de, Bresser P, Zee JS van der, Jansen HM, Spek CA, Poll T van der (2006) Toll-like receptor mRNA levels in alveolar macrophages after inhalation of endotoxin. Eur Respir J 28:622–626

    CAS  PubMed  Google Scholar 

  • Matute-Bello G, Lee JS, Frevert CW, Liles WC, Sutlief S, Ballman K, Wong V, Selk A, Martin TR (2004) Optimal timing to repopulation of resident alveolar macrophages with donor cells following total body irradiation and bone marrow transplantation in mice. J Immunol Methods 292:25–34

    CAS  PubMed  Google Scholar 

  • Maus UA, Janzen S, Wall G, Srivastava M, Blackwell TS, Christman JW, Seeger W, Welte T, Lohmeyer J (2006) Resident alveolar macrophages are replaced by recruited monocytes in response to endotoxin-induced lung inflammation. Am J Respir Cell Mol Biol 35:227–235

    CAS  PubMed  Google Scholar 

  • Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397

    CAS  PubMed  Google Scholar 

  • Muneta Y, Uenishi H, Kikuma R, Yoshihara K, Shimoji Y, Yamamoto R, Hamashima N, Yokomizo Y, Mori Y (2003) Porcine TLR2 and TLR6: identification and their involvement in Mycoplasma hyopneumoniae infection. J Interferon Cytokine Res 23:583–590

    CAS  PubMed  Google Scholar 

  • Murphy J, Summer R, Wilson AA, Kotton DN, Fine A (2008) The prolonged life-span of alveolar macrophages. Am J Respir Cell Mol Biol 38:380–385

    CAS  PubMed  Google Scholar 

  • Naito M, Hasegawa G, Takahashi K (1997) Development, differentiation, and maturation of Kupffer cells. Microsc Res Tech 39:350–364

    CAS  PubMed  Google Scholar 

  • O'Mahony DS, Pham U, Iyer R, Hawn TR, Liles WC (2008) Differential constitutive and cytokine-modulated expression of human Toll-like receptors in primary neutrophils, monocytes, and macrophages. Int J Med Sci 5:1–8

    PubMed  Google Scholar 

  • Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T (2003) TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 4:161–167

    CAS  PubMed  Google Scholar 

  • Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 97:13766–13771

    CAS  PubMed  Google Scholar 

  • Parbhakar OP, Duke T, Townsend HG, Singh B (2005) Depletion of pulmonary intravascular macrophages partially inhibits lipopolysaccharide-induced lung inflammation in horses. Vet Res 36:557–569

    PubMed  Google Scholar 

  • Pastva AM, Wright JR, Williams KL (2007) Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc 4:252–257

    CAS  PubMed  Google Scholar 

  • Platz J, Beisswenger C, Dalpke A, Koczulla R, Pinkenburg O, Vogelmeier C, Bals R (2004) Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J Immunol 173:1219–1223

    CAS  PubMed  Google Scholar 

  • Prieditis H, Adamson IYR (1996) Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury. J Leukoc Biol 59:534–538

    CAS  PubMed  Google Scholar 

  • Punturieri A, Alviani RS, Polak T, Copper P, Sonstein J, Curtis JL (2004) Specific engagement of TLR4 or TLR3 does not lead to IFN-beta-mediated innate signal amplification and STAT1 phosphorylation in resident murine alveolar macrophages. J Immunol 173:1033–1042

    CAS  PubMed  Google Scholar 

  • Rankin R, Pontarollo R, Ioannou X, Krieg AM, Hecker R, Babiuk LA, Drunen Littel-van den Hurk S van (2001) CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved. Antisense Nucleic Acid Drug Dev 11:333–340

    CAS  PubMed  Google Scholar 

  • Raymond CR, Wilkie BN (2005) Toll-like receptor, MHC II, B7 and cytokine expression by porcine monocytes and monocyte-derived dendritic cells in response to microbial pathogen-associated molecular patterns. Vet Immunol Immunopathol 107:235–247

    CAS  PubMed  Google Scholar 

  • Reidy MF, Wright JR (2003) Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by inflammatory alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 285:L854–L861

    CAS  PubMed  Google Scholar 

  • Remer KA, Reimer T, Brcic M, Jungi TW (2005) Evidence for involvement of peptidoglycan in the triggering of an oxidative burst by Listeria monocytogenes in phagocytes. Clin Exp Immunol 140:73–80

    CAS  PubMed  Google Scholar 

  • Rossignol DP, Lynn M (2005) TLR4 antagonists for endotoxemia and beyond. Curr Opin Investig Drugs 6:496–502

    CAS  PubMed  Google Scholar 

  • Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, Bauer S (2004) Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol 34:2541–2550

    CAS  PubMed  Google Scholar 

  • Salez L, Balloy V, Rooijen N van, Lebastard M, Touqui L, McCormack FX, Chignard M (2001) Surfactant protein A suppresses lipopolysaccharide-induced IL-10 production by murine macrophages. J Immunol 166:6376–6382

    CAS  PubMed  Google Scholar 

  • Sawyer RT, Strausbauch PH, Volkman A (1982) Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89. Lab Invest 46:165–170

    CAS  PubMed  Google Scholar 

  • Schneberger D, Caldwell S, Suri SS, Singh B (2009) Expression of toll-like receptor 9 in horse lungs. Anat Rec 292:1068–1077

    CAS  Google Scholar 

  • Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ (1999) Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 274:17406–17409

    CAS  PubMed  Google Scholar 

  • Serbina NV, Jia T, Hohl TM, Pamer EG (2008) Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 26:421–452

    CAS  PubMed  Google Scholar 

  • Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131–E136

    CAS  PubMed  Google Scholar 

  • Silva Correia J da, Soldau K, Christen U, Tobias PS, Ulevitch RJ (2001) Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. Transfer from CD14 to TLR4 and MD-2. J Biol Chem 276:21129–21135

    PubMed  Google Scholar 

  • Singh B, Pearce JW, Gamage LN, Janardhan K, Caldwell S (2004) Depletion of pulmonary intravascular macrophages inhibits acute lung inflammation. Am J Physiol Lung Cell Mol Physiol 286:L363–L372

    CAS  PubMed  Google Scholar 

  • Singh Suri S, Janardhan KS, Parbhakar O, Caldwell S, Appleyard G, Singh B (2006) Expression of toll-like receptor 4 and 2 in horse lungs. Vet Res 37:541–551

    PubMed  Google Scholar 

  • Siren J, Pirhonen J, Julkunen I, Matikainen S (2005) IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29. J Immunol 174:1932–1937

    CAS  PubMed  Google Scholar 

  • Smith KD, Andersen-Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, Cookson BT, Aderem A (2003) Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol 4:1247–1253

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Staub NC (1994) Pulmonary intravascular macrophages. Annu Rev Physiol 56:47–67

    CAS  PubMed  Google Scholar 

  • Steinman RM, Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137:1142–1162

    CAS  PubMed  Google Scholar 

  • Steinmüller C, Franke-Ullmann G, Lohmann-Matthes M-L, Emmendörffer A (2000) Local activation of nonspecific defense against a respiratory model infection by application of interferon-γ. Am J Respir Cell Mol Biol 22:481–490

    PubMed  Google Scholar 

  • Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376

    CAS  PubMed  Google Scholar 

  • Takeuchi O, Kaufmann A, Grote K, Kawai T, Hoshino K, Morr M, Muhlradt PF, Akira S (2000) Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pathway. J Immunol 164:554–557

    CAS  PubMed  Google Scholar 

  • Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13:933–940

    CAS  PubMed  Google Scholar 

  • Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL, Akira S (2002) Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol 169:10–14

    CAS  PubMed  Google Scholar 

  • Taut K, Winter C, Briles DE, Paton JC, Christman JW, Maus R, Baumann R, Welte T, Maus UA (2008) Macrophage turnover kinetics in the lungs of mice infected with Streptococcus pneumoniae. Am J Respir Cell Mol Biol 38:105–113

    CAS  PubMed  Google Scholar 

  • Thoma-Uszynski S, Stenger S, Takeuchi O, Ochoa MT, Engele M, Sieling PA, Barnes PF, Rollinghoff M, Bolcskei PL, Wagner M, Akira S, Norgard MV, Belisle JT, Godowski PJ, Bloom BR, Modlin RL (2001) Induction of direct antimicrobial activity through mammalian toll-like receptors. Science 291:1544–1547

    CAS  PubMed  Google Scholar 

  • Toka FN, Nfon CK, Dawson H, Golde WT (2009) Accessory-cell-mediated activation of porcine NK cells by toll-like receptor 7 (TLR7) and TLR8 agonists. Clin Vaccine Immunol 16:866–878

    CAS  PubMed  Google Scholar 

  • Tschernig T, Pabst R (2009) What is the clinical relevance of different lung compartments? Pulm Med 9:39–42

    Google Scholar 

  • Underhill DM, Ozinsky A, Hajjar AM, Stevens A, Wilson CB, Bassetti M, Aderem A (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401:811–815

    CAS  PubMed  Google Scholar 

  • Van Furth R, Cohn ZA (1968) The origin and kinetics of mononuclear phagocytes. J Exp Med 128:415–435

    PubMed  Google Scholar 

  • Van Furth R, Thompson J (1971) Review of the origin and kinetics of the promonocytes, monocytes, and macrophages and a brief discussion of the mononuclear phagocyte system. Ann Inst Pasteur (Paris) 120:337–355

    Google Scholar 

  • Visintin A, Mazzoni A, Spitzer JH, Wyllie DH, Dower SK, Segal DM (2001) Regulation of Toll-like receptors in human monocytes and dendritic cells. J Immunol 166:249–255

    CAS  PubMed  Google Scholar 

  • Warner AE, Brain JD (1990) The cell biology and pathogenic role of pulmonary intravascular macrophages. Am J Physiol 258:L1–L12

    CAS  PubMed  Google Scholar 

  • Wassef A, Janardhan K, Pearce JW, Singh B (2004) Toll-like receptor 4 in normal and inflamed lungs and other organs of pig, dog and cattle. Histol Histopathol 19:1201–1208

    CAS  PubMed  Google Scholar 

  • Weber C, Belge KU, Hundelshausen P von, Draude G, Steppich B, Mack M, Frankenberger M, Weber KS, Ziegler-Heitbrock HW (2000) Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 67:699–704

    CAS  PubMed  Google Scholar 

  • Werling D, Hope JC, Howard CJ, Jungi TW (2004) Differential production of cytokines, reactive oxygen and nitrogen by bovine macrophages and dendritic cells stimulated with Toll-like receptor agonists. Immunology 111:41–52

    CAS  PubMed  Google Scholar 

  • Werling D, Piercy J, Coffey TJ (2006) Expression of TOLL-like receptors (TLR) by bovine antigen-presenting cells-potential role in pathogen discrimination? Vet Immunol Immunopathol 112:2–11

    CAS  PubMed  Google Scholar 

  • Wyllie DH, Kiss-Toth E, Visintin A, Smith SC, Boussouf S, Segal DM, Duff GW, Dower SK (2000) Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses. J Immunol 165:7125–7132

    CAS  PubMed  Google Scholar 

  • Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, Takeda K, Akira S (2002a) Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420:324–329

    CAS  PubMed  Google Scholar 

  • Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S (2002b) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169:6668–6672

    CAS  PubMed  Google Scholar 

  • Zarember KA, Godowski PJ (2002) Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol 168:554–561

    CAS  PubMed  Google Scholar 

  • Zhang Y, Shoda LK, Brayton KA, Estes DM, Palmer GH, Brown WC (2001) Induction of interleukin-6 and interleukin-12 in bovine B lymphocytes, monocytes, and macrophages by a CpG oligodeoxynucleotide (ODN 2059) containing the GTCGTT motif. J Interferon Cytokine Res 21:871–881

    CAS  PubMed  Google Scholar 

  • Ziegler-Heitbrock HW, Fingerle G, Strobel M, Schraut W, Stelter F, Schutt C, Passlick B, Pforte A (1993) The novel subset of CD14+/CD16+ blood monocytes exhibits features of tissue macrophages. Eur J Immunol 23:2053–2058

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada

    David Schneberger & Baljit Singh

  2. Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

    Karin Aharonson-Raz

Authors
  1. David Schneberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karin Aharonson-Raz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baljit Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Baljit Singh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schneberger, D., Aharonson-Raz, K. & Singh, B. Monocyte and macrophage heterogeneity and Toll-like receptors in the lung. Cell Tissue Res 343, 97–106 (2011). https://doi.org/10.1007/s00441-010-1032-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-010-1032-2

Keywords

Search

Navigation