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  • Print publication year: 2007
  • Online publication date: August 2009

5 - Role of dendritic cells in the innate response to bacteria

from II - Dendritic cells and innate immune responses to bacteria



Innate immunity is an ancient and highly conserved system that provides the first line of defense upon encounter with pathogenic organisms. Activation of innate immune responses is a complex process involving multiple components and distinct steps. The cellular components of innate immunity include neutrophils, monocytes, macrophages and dendritic cells (DCs). These cells are capable of direct microbicidal activity that partially depends on inducible nitric synthase (iNOS) and NADPH oxidase complex that catalyze production of toxic anti-microbial compounds. Additionally, they secrete a vast array of pro-inflammatory mediators such as cytokines and chemokines and can recruit and activate other inflammatory cells, thus amplifying the immune cascade. Apart from their role in restricting microbial growth, innate immune responses also provide the inflammatory context in which adaptive T- and B-cell immune responses develop.

Dendritic cells are derived from hematopoietic progenitor cells in the bone marrow and are found in the peripheral circulation as well as in the lymphoid and non-lymphoid tissues. Dendritic cells can be subdivided into several subsets based on the expression of the cell surface markers and different subsets have been ascribed distinct functions during the immune response. Since their discovery, dendritic cells have been studied extensively with regard to their role as antigen-presenting cells. However, it is becoming increasingly clear that dendritic cells also play an important role during the innate immune responses to microbial pathogens.

Taylor, P. al. (2005). Macrophage receptors and immune recognition. Annu. Rev. Immunol. 23, 901–44
Segal, A. W. (2005). How neutrophils kill microbes. Annu. Rev. Immunol. 23, 197–223
Shortman, K. and Liu, Y. J. (2002). Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2(3), 151–61
Steinman, R. M. (1991). The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–96
Carbone, F. R., Belz, G. T., and Heath, W. R. (2004). Transfer of antigen between migrating and lymph node-resident dendritic cells in peripheral T-cell tolerance and immunity. Trends Immunol. 25(12), 655–8
Rescigno, al. (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2(4), 361–7
Lambrecht, B. N., Prins, J. B., and Hoogsteden, H. C. (2001). Lung dendritic cells and host immunity to infection. Eur. Respir. J. 18(4), 692–704
Vazquez-Torres, al. (1999). Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401(6755), 804–8
Gonzalez-Juarrero, M. and Orme, I. M. (2001). Characterization of murine lung dendritic cells infected with Mycobacterium tuberculosis. Infect. Immun. 69(2), 1127–33
Pedroza-Gonzalez, al. (2004). In situanalysis of lung antigen-presenting cells during murine pulmonary infection with virulentMycobacterium tuberculosis. Int. J. Exp. Pathol. 85(3), 135–45
Iwasaki, A. and Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5(10), 987–95
Fritz, J. al. (2005). Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and nucleotide-binding oligomerization domain1- and nucleotide-binding oligomerization domain2-activating agonists. Eur. J. Immunol. 35(8), 2459–70
Gutierrez, al. (2002). Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J. Biol. Chem. 277(44), 41701–5
Gellin, B. G. and Broome, C. V. (1989). Listeriosis. JAMA 261(9), 1313–20
Gaillard, J. al. (1991). Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci. Cell 65(7), 1127–41
Dramsi, al. (1995). Entry of Listeria monocytogenes into hepatocytes requires expression of inIB, a surface protein of the internalin multigene family. Mol. Microbiol. 16(2), 251–61
Braun, L., Ghebrehiwet, B., and Cossart, P. (2000). gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein ofListeria monocytogenes. EMBO J. 19(7), 1458–66
Shen, al. (2000). InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase. Cell 103(3), 501–10
Marino, al. (2002). GW domains of the Listeria monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands. EMBO J. 21(21), 5623–34
Jonquieres, R., Pizarro-Cerda, J., and Cossart, P. (2001). Synergy between the N- and C-terminal domains of InlB for efficient invasion of non-phagocytic cells by Listeria monocytogenes. Mol. Microbiol. 42(4), 955–65
Dunne, D. al. (1994). The type I macrophage scavenger receptor binds to Gram-positive bacteria and recognizes lipoteichoic acid. Proc. Natl Acad. Sci. U S A 91(5), 1863–7
Drevets, D. A. and Campbell, P. A. (1991). Roles of complement and complement receptor type 3 in phagocytosis of Listeria monocytogenes by inflammatory mouse peritoneal macrophages. Infect. Immun. 59(8), 2645–52
Bielecki, al. (1990). Bacillus subtilis expressing a haemolysin gene from Listeria monocytogenes can grow in mammalian cells. Nature 345(6271), 175–6
O'Riordan, al. (2002). Innate recognition of bacteria by a macrophage cytosolic surveillance pathway. Proc. Natl Acad. Sci. U S A 99(21), 13861–6
Serbina, N. al. (2003). Sequential MyD88-independent and -dependent activation of innate immune responses to intracellular bacterial infection. Immunity 19(6), 891–901
Berche, P., Gaillard, J. L., and Sansonetti, P. J. (1987). Intracellular growth of Listeria monocytogenes as a prerequisite for in vivo induction of T cell-mediated immunity. J. Immunol. 138(7), 2266–71
Domann, al. (1992). A novel bacterial virulence gene in Listeria monocytogenes required for host cell microfilament interaction with homology to the proline-rich region of vinculin. EMBO J. 11(5), 1981–90
Kocks, al. (1992). L. monocytogenes-induced actin assembly requires the actA gene product, a surface protein. Cell 68(3), 521–31
Goossens, P. L. and Milon, G. (1992). Induction of protective CD8+ T lymphocytes by an attenuated Listeria monocytogenes actA mutant. Int. Immunol. 4(12), 1413–18
Harty, J. T. and Bevan, M. J. (1996). CD8 T-cell recognition of macrophages and hepatocytes results in immunity to Listeria monocytogenes. Infect. Immun. 64(9), 3632–40
Bancroft, G. J., Schreiber, R. D., and Unanue, E. R. (1991). Natural immunity: a T-cell-independent pathway of macrophage activation, defined in the scid mouse. Immunol. Rev. 124, 5–24
Stevenson, M. M., Kongshavn, P. A., and Skamene, E. (1981). Genetic linkage of resistance to Listeria monocytogenes with macrophage inflammatory responses. J. Immunol. 127(2), 402–7
Cheers, C. and McKenzie, I. F. (1978). Resistance and susceptibility of mice to bacterial infection: genetics of listeriosis. Infect. Immun. 19(3), 755–62
Boyartchuk, al. (2004). The host resistance locus sst1 controls innate immunity to Listeria monocytogenes infection in immunodeficient mice. J. Immunol. 173(8), 5112–20
Gervais, F., Desforges, C., and Skamene, E. (1989). The C5-sufficient A/J congenic mouse strain. Inflammatory response and resistance to Listeria monocytogenes. J. Immunol. 142(6), 2057–60
Gervais, F., Stevenson, M., and Skamene, E. (1984). Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus. J. Immunol. 132(4), 2078–83
Unanue, E. R. (1997). Studies in listeriosis show the strong symbiosis between the innate cellular system and the T-cell response. Immunol. Rev. 158, 11–25
Nickol, A. D. and Bonventre, P. F. (1977). Anomalous high native resistance to athymic mice to bacterial pathogens. Infect. Immun. 18(3), 636–45
Buchmeier, N. A. and Schreiber, R. D. (1985). Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc. Natl Acad. Sci. U S A 82(21), 7404–8
Havell, E. A. (1989). Evidence that tumor necrosis factor has an important role in antibacterial resistance. J. Immunol. 143(9), 2894–9
Pfeffer, al. (1993). Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73(3), 457–67
Rothe, al. (1993). Mice lacking the tumour necrosis factor receptor 1 are resistant to Tnuclear factor-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364(6440), 798–802
Harty, J. T. and Bevan, M. J. (1995). Specific immunity to Listeria monocytogenes in the absence of interferon gamma. Immunity 3(1), 109–17
Andersson, al. (1998). Early interferon-gamma production and innate immunity during Listeria monocytogenes infection in the absence of natural killer cells. J. Immunol. 161(10), 5600–6
Xanthoulea, al. (2004). Tumor necrosis factor (Tnuclear factor) receptor shedding controls thresholds of innate immune activation that balance opposing Tnuclear factor functions in infectious and inflammatory diseases. J. Exp. Med. 200(3), 367–76
Tripp, C. al. (1994). Neutralization of interleukin-12 decreases resistance to Listeria in SCID and C.B-17 mice. Reversal by interferon-gamma. J. Immunol. 152(4), 1883–7
Neighbors, al. (2001). A critical role for interleukin 18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on interferon gamma production. J. Exp. Med. 194(3), 343–54
Carrero, J. A., Calderon, B., and Unanue, E. R. (2004). Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to listeria infection. J. Exp. Med. 200(4), 535–40
O'Connell, R. al. (2004). Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J. Exp. Med. 200(4), 437–45
Auerbuch, al. (2004). Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J. Exp. Med. 200(4), 527–33
Beckerman, K. al. (1993). Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes. J. Immunol. 150(3), 888–95
Conlan, J. W. and North, R. J. (1994). Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody. J. Exp. Med. 179(1), 259–68
Rogers, H. W. and Unanue, E. R. (1993). Neutrophils are involved in acute, nonspecific resistance to Listeria monocytogenes in mice. Infect. Immun. 61(12), 5090–6
Czuprynski, C. al. (1994). Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection. J. Immunol. 152(4), 1836–46
Rosen, H., Gordon, S., and North, R. J. (1989). Exacerbation of murine listeriosis by a monoclonal antibody specific for the type 3 complement receptor of myelomonocytic cells. Absence of monocytes at infective foci allows Listeria to multiply in nonphagocytic cells. J. Exp. Med. 170(1), 27–37
Fang, F. C. (2004). Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat. Rev. Microbiol. 2(10), 820–32
Amer, A. O. and Swanson, M. S. (2002). A phagosome of one's own: a microbial guide to life in the macrophage. Curr. Opin. Microbiol. 5(1), 56–61
Shiloh, M. al. (1999). Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. Immunity 10(1), 29–38
Serbina, N. al. (2003). Tnuclear factor/inducible nitric oxide synthase-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19(1), 59–70
Endres, al. (1997). Listeriosis in p47(phox−/−) and TRp55−/− mice: protection despite absence of ROI and susceptibility despite presence of RNI. Immunity 7(3), 419–32
Dinauer, M. C., Deck, M. B., and Unanue, E. R. (1997). Mice lacking reduced nicotinamide adenine dinucleotide phosphate oxidase activity show increased susceptibility to early infection with Listeria monocytogenes. J. Immunol. 158(12), 5581–3
Kuziel, W. al. (1997). Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc. Natl Acad. Sci. U S A 94(22), 12053–8
Kurihara, al. (1997). Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J. Exp. Med. 186(10), 1757–62
Sato, al. (2000). CC chemokine receptor (CCR)2 is required for Langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J. Exp. Med. 192(2), 205–18
Izikson, al. (2000). Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J. Exp. Med. 192(7), 1075–80
Vecchi, al. (1999). Differential responsiveness to constitutive vs. inducible chemokines of immature and mature mouse dendritic cells. J. Leukoc. Biol. 66(3), 489–94
Mack, al. (2001). Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. J. Immunol. 166(7), 4697–704
Merad, al. (2002). Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3(12), 1135–41
Geissmann, F., Jung, S., and Littman, D. R. (2003). Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1), 71–82
Peters, al. (2004). CCR2-dependent trafficking of F4/80dim macrophages and CD11cdim/intermediate dendritic cells is crucial for T cell recruitment to lungs infected with Mycobacterium tuberculosis. J. Immunol. 172(12), 7647–53
Kurihara, T. and Bravo, R. (1996). Cloning and functional expression of mCCR2, a murine receptor for the C–C chemokines JE and FIC. J. Biol. Chem. 271(20), 11603–7
Sozzani, al. (1997). Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. J. Immunol. 159(4), 1993–2000
Sheffler, L. al. (1995). Exogenous nitric oxide regulates interferon-gamma plus lipopolysaccharide-induced nitric oxide synthase expression in mouse macrophages. J. Immunol. 155(2), 886–94
Lu, al. (1996). Induction of nitric oxide synthase in mouse dendritic cells by interferon-gamma, endotoxin, and interaction with allogeneic T cells: nitric oxide production is associated with dendritic cell apoptosis. J. Immunol. 157(8), 3577–86
Albina, J. E. and Henry, W. L. Jr. (1991). Suppression of lymphocyte proliferation through the nitric oxide synthesizing pathway. J. Surg. Res. 50(4), 403–9
Eriksson, S., Chambers, B. J., and Rhen, M. (2003). Nitric oxide produced by murine dendritic cells is cytotoxic for intracellular Salmonella enterica sv. Typhimurium. Scand. J. Immunol. 58(5), 493–502
Cheminay, C., Mohlenbrink, A., and Hensel, M. (2005). Intracellular Salmonella inhibit antigen presentation by dendritic cells. J. Immunol. 174(5), 2892–9
Fremond, C. al. (2004). Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. J. Clin. Invest. 114(12), 1790–9
Bodnar, K. A., Serbina, N. V., and Flynn, J. L. (2001). Fate of Mycobacterium tuberculosis within murine dendritic cells. Infect. Immun. 69(2), 800–9
Buettner, al. (2005). Inverse correlation of maturity and antibacterial activity in human dendritic cells. J. Immunol. 174(7), 4203–9
Kolb-Maurer, al. (2000). Listeria monocytogenes-infected human dendritic cells: uptake and host cell response. Infect. Immun. 68(6), 3680–8
Paschen, al. (2000). Human dendritic cells infected by Listeria monocytogenes: induction of maturation, requirements for phagolysosomal escape and antigen presentation capacity. Eur. J. Immunol. 30(12), 3447–56
Guzman, C. al. (1995). Interaction of Listeria monocytogenes with mouse dendritic cells. Infect. Immun. 63(9), 3665–73
Neild, A. L. and Roy, C. R. (2003). Legionella reveal dendritic cell functions that facilitate selection of antigens for major histocompatibility complex class II presentation. Immunity 18(6), 813–23
Macpherson, A. J. and Uhr, T. (2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303(5664), 1662–5
Hopkins, S. al. (2000). A recombinant Salmonella typhimurium vaccine strain is taken up and survives within murine Peyer's patch dendritic cells. Cell Microbiol. 2(1), 59–68
Brzoza, K. L., Rockel, A. B., and Hiltbold, E. M. (2004). Cytoplasmic entry of Listeria monocytogenes enhances dendritic cell maturation and T cell differentiation and function. J. Immunol. 173(4), 2641–51
Feng, al. (2005). Listeria-infected myeloid dendritic cells produce interferon-beta, priming T cell activation. J. Immunol. 175(1), 421–32
Kolb-Maurer, al. (2003). Production of interleukin-12 and interleukin-18 in human dendritic cells upon infection by Listeria monocytogenes. FEMS Immunol. Med. Microbiol. 35(3), 255–62
Takeda, K. and Akira, S. (2004). Toll-like receptor signaling pathways. Semin. Immunol. 16(1), 3–9
Seki, al. (2002). Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J. Immunol. 169(7), 3863–8
Edelson, B. T. and Unanue, E. R. (2002). MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity. J. Immunol. 169(7), 3869–75
Adachi, al. (1998). Targeted disruption of the MyD88 gene results in loss of interleukin-1- and interleukin-18-mediated function. Immunity 9(1), 143–50
Tsuji, N. al. (2004). Roles of caspase-1 in Listeria infection in mice. Int. Immunol. 16(2), 335–43
Hayashi, al. (2001). The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410(6832), 1099–103
Ito, al. (2005). CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection. J. Immunol. 174(2), 777–82
Inohara, al. (2003). Host recognition of bacterial muramyl dipeptide mediated through nucleotide-binding oligomerization domain2. Implications for Crohn's disease. J. Biol. Chem. 278(8), 5509–12
Girardin, S. al. (2003). Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (muramyl dipeptide) detection. J. Biol. Chem. 278(11), 8869–72
Li, al. (2004). Regulation of interleukin-8 and interleukin-1beta expression in Crohn's disease associated nucleotide-binding oligomerization domain2/CARD15 mutations. Hum. Mol. Genet. 13(16), 1715–25
Girardin, S. al. (2003). Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science 300(5625), 1584–7
Kobayashi, K. al. (2005). Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307(5710), 731–4
Chin, A. al. (2002). Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature 416(6877), 190–4
Kobayashi, al. (2002). Rip-like interacting caspase-like apoptosis-regulatory protein kinase/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416(6877), 194–9
Hauf, al. (1997). Listeria monocytogenes infection of P388D1 macrophages results in a biphasic nuclear factor-kappaB (RelA/p50) activation induced by lipoteichoic acid and bacterial phospholipases and mediated by IkappaBalpha and IkappaBbeta degradation. Proc. Natl Acad. Sci. U S A 94(17), 9394–9
O'Connell, R. al. (2005). Immune activation of type I interferons by Listeria monocytogenes occurs independently of Toll-like receptor4, Toll-like receptor2, and receptor interacting protein 2 but involves Tnuclear factorR-associated nuclear factor kappa B kinase-binding kinase 1. J. Immunol. 174(3), 1602–7
Pron, al. (2001). Dendritic cells are early cellular targets of Listeria monocytogenes after intestinal delivery and are involved in bacterial spread in the host. Cell Microbiol. 3(5), 331–40
Vollstedt, al. (2003). Flt3 ligand-treated neonatal mice have increased innate immunity against intracellular pathogens and efficiently control virus infections. J. Exp. Med. 197(5), 575–84
Jung, al. (2002). In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity 17(2), 211–20
Kolb-Maurer, al. (2003). Induction of interleukin-12 and interleukin-18 in human dendritic cells upon infection byListeria monocytogenes. FEMS Immunol. Med. Microbiol. 35(3), 255–62
Alanir, R. al. (2004). Increased dendritic cell numbers impair protective immunity to intracellular bacteria despite augmenting antigen-specific CD8+ T lymphocyte responses. J. Immunol. 172, 3725–35