Skip to main content Accessibility help
  • Print publication year: 2007
  • Online publication date: August 2009

7 - Peculiar ability of dendritic cells to process and present antigens from vacuolar pathogens: a lesson from Legionella

from III - Dendritic cells and adaptive immune responses to bacteria



Legionella pneumophila is a Gram-negative facultative intracellular pathogen capable of growing in both protozoan and mammalian host cells. L. pneumophila is found in natural and artificial water reservoirs and less often in soil and organic matter (Fields, 1996; Szymanska et al., 2004). Optimal proliferation conditions for Legionella are those in which water temperatures are between 25°C and 42°C, calcium and magnesium salt-containing sediments are present, and are further enhanced by the presence of algae and protozoa (Szymanska et al., 2004). In hostile conditions, Legionella and other organisms become attached to surfaces in an aquatic environment, forming a biofilm (Langmark et al., 2005). L. pneumophila can be isolated from such natural water sources as lakes, ponds and streams; however, artificial reservoirs such as plumbing fixtures, hot water tanks, whirlpool spas and cooling towers, all possess excellent conditions for Legionella proliferation inside protozoan hosts and are the source of most outbreaks (Fliermans et al., 1981; Yee and Wadowsky, 1982).

The first recognized outbreak of L. pneumophila occurred in Philadelphia in 1976 during a state convention of the American Legion (Fraser et al., 1977). During this outbreak a total of 221 people contracted the disease, 34 of whom subsequently died. A new Gram-negative bacterium was isolated from both patients and the air-conditioning system of the hotel that was the source of the outbreak (McDade et al., 1977). This isolated organism was named Legionella pneumophila (Brenner et al., 1979). There are 48 different species of Legionella found in nature.

Akamine, M., Higa, al. (2005). Differential roles of Toll-like receptors 2 and 4 in in vitro responses of macrophages to Legionella pneumophila. Infect. Immun. 73(1), 352–61
Bhardwaj, N., Nash, T. al. (1986). Interferon-gamma-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila. J. Immunol. 137(8), 2662–9
Blanchard, D. K., Friedman, al. (1988). Role of gamma interferon in induction of natural killer activity by Legionella pneumophila in vitro and in an experimental murine infection model. Infect. Immun. 56(5), 1187–93
Breiman, R. F. and Horwitz, M. A. (1987). Guinea pigs sublethally infected with aerosolized Legionella pneumophila develop humoral and cell-mediated immune responses and are protected against lethal aerosol challenge. A model for studying host defense against lung infections caused by intracellular pathogens. J. Exp. Med. 165(3), 799–811
Brenner, D. J., Steigerwalt, A. al. (1979). Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, species nova, of the family Legionellaceae, familia nova. Ann. Intern. Med. 90(4), 656–8
Brieland, J., Freeman, al. (1994). Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease. Am. J. Pathol. 145(6), 1537–46
Brieland, J. K., Heath, L. al. (1996). Humoral immunity and regulation of intrapulmonary growth of Legionella pneumophila in the immunocompetent host. J. Immunol. 157(11), 5002–8
Brieland, J. K., Remick, D. al. (1995). In vivo regulation of replicative Legionella pneumophila lung infection by endogenous tumor necrosis factor alpha and nitric oxide. Infect. Immun. 63(9), 3253–8
Byrd, T. F. and Horwitz, M. A. (1989). Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J. Clin. Invest. 83(5), 1457–65
Byrd, T. F. and Horwitz, M. A. (1991). Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila. J. Clin. Invest. 88(4), 1103–12
Chen, J., Felipe, K. al. (2004). Legionella effectors that promote nonlytic release from protozoa. Science 303(5662), 1358–61
Deng, J. C., Tateda, al. (2001). Transient transgenic expression of gamma interferon promotes Legionella pneumophila clearance in immunocompetent hosts. Infect. Immun. 69(10), 6382–90
Derre, I. and Isberg, R. R. (2004). Macrophages from mice with the restrictive Lgn1 allele exhibit multifactorial resistance to Legionella pneumophila. Infect. Immun. 72(11), 6221–9
Diez, E., Lee, S. al. (2003). Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila. Nat. Genet. 33(1), 55–60
Fields, B. S. (1996). The molecular ecology of Legionellae. Trends Microbiol. 4(7), 286–90
Fliermans, C. B., Cherry, W. al. (1981). Ecological distribution of Legionella pneumophila. Appl. Environ. Microbiol. 41(1), 9–16
Fraser, D. W., Tsai, T. al. (1977). Legionnaires' disease: description of an epidemic of pneumonia. N. Engl. J. Med. 297(22), 1189–97
Girard, R., Pedron, al. (2003). Lipopolysaccharides from Legionella and Rhizobium stimulate mouse bone marrow granulocytes via Toll-like receptor 2. J. Cell Sci. 116(Pt 2), 293–302
Hawn, T. R., Verbon, al. (2003). A common dominant Toll-like receptor5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. J. Exp. Med. 198(10), 1563–72
Heath, L., Chrisp, al. (1996). Effector mechanisms responsible for gamma interferon-mediated host resistance to Legionella pneumophila lung infection: the role of endogenous nitric oxide differs in susceptible and resistant murine hosts. Infect. Immun. 64(12), 5151–60
Horwitz, M. A. (1983). Formation of a novel phagosome by the Legionnaires' disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 158(4), 1319–31
Horwitz, M. A. (1987). Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes. J. Exp. Med. 166(5), 1310–28
Horwitz, M. A. and Silverstein, S. C. (1981). Interaction of the legionnaires' disease bacterium (Legionella pneumophila) with human phagocytes. II. Antibody promotes binding of L. pneumophila to monocytes but does not inhibit intracellular multiplication. J. Exp. Med. 153(2), 398–406
Inohara, N., Chamaillard, al. (2005). nucleotide-binding oligomerization domain-leucine-rich repeat proteins: role in host–microbial interactions and inflammatory disease. Annu. Rev. Biochem. 74: 355–83
Kagan, J. C. and Roy, C. R. (2002). Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat. Cell Biol. 4(12), 945–54
Kikuchi, T., Kobayashi, al. (2004). Dendritic cells pulsed with live and dead Legionella pneumophila elicit distinct immune responses. J. Immunol. 172(3), 1727–34
Klein, T. W., Yamamoto, al. (1991). Interferon-gamma induced resistance to Legionella pneumophila in susceptible A/J mouse macrophages. J. Leukoc. Biol. 49(1), 98–103
Langmark, J., Storey, M. al. (2005). Accumulation and fate of microorganisms and microspheres in biofilms formed in a pilot-scale water distribution system. Appl. Environ. Microbiol. 71(2), 706–12
Luo, Z. Q. and Isberg, R. R. (2004). Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc. Natl Acad. Sci. U S A 101(3), 841–6
Marra, A., Blander, S. al. (1992). Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc. Natl Acad. Sci. U S A 89(20), 9607–11
McDade, J. E., Shepard, C. al. (1977). Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N. Engl. J. Med. 297(22), 1197–203
Nagai, H., Kagan, J. al. (2002). A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 295(5555), 679–82
Nash, T. W., Libby, D. al. (1988). interferon-gamma-activated human alveolar macrophages inhibit the intracellular multiplication of Legionella pneumophila. J. Immunol. 140(11), 3978–81
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
Neild, A. L. and Roy, C. R. (2004). Immunity to vacuolar pathogens: what can we learn from Legionella?Cell Microbiol. 6(11), 1011–18
Park, D. R. and Skerrett, S. J. (1996). interleukin-10 enhances the growth of Legionella pneumophila in human mononuclear phagocytes and reverses the protective effect of interferon-gamma: differential responses of blood monocytes and alveolar macrophages. J. Immunol. 157(6), 2528–38
Roy, C. R. and Tilney, L. G. (2002). The road less traveled: transport of Legionella to the endoplasmic reticulum. J. Cell Biol. 158(3), 415–19
Saito, M., Kajiwara, al. (2001). Fate of Legionella pneumophila in macrophages of C57BL/6 chronic granulomatous disease mice. Microbiol. Immunol. 45(7), 539–41
Salins, S., Newton, al. (2001). Differential induction of gamma interferon in Legionella pneumophila-infected macrophages from BALB/c and A/J mice. Infect. Immun. 69(6), 3605–10
Santic, M., Molmeret, al. (2005). Maturation of the Legionella pneumophila-containing phagosome into a phagolysosome within gamma interferon-activated macrophages. Infect. Immun. 73(5), 3166–71
Schaible, U. E., Sturgill-Koszycki, al. (1998). Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages. J. Immunol. 160(3), 1290–6
Schiavoni, G., Mauri, al. (2004). Type I interferon protects permissive macrophages from Legionella pneumophila infection through an interferon-gamma-independent pathway. J. Immunol. 173(2), 1266–75
Segal, G., Purcell, al. (1998). Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc. Natl Acad. Sci. U S A 95(4), 1669–74
Shinozawa, Y., Matsumoto, al. (2002). Role of interferon-gamma in inflammatory responses in murine respiratory infection with Legionella pneumophila. J. Med. Microbiol. 51(3), 225–30
Smith, K. D., Andersen-Nissen, al. (2003). Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat. Immunol. 4(12), 1247–53
Susa, M., Ticac, al. (1998). Legionella pneumophila infection in intratracheally inoculated T cell-depleted or -nondepleted A/J mice. J. Immunol. 160(1), 316–21
Szymanska, J., Wdowiak, al. (2004). Microbial quality of water in dental unit reservoirs. Ann. Agric. Environ. Med. 11(2), 355–8
Tateda, K., Matsumoto, al. (1998). Serum cytokines in patients with Legionella pneumonia: relative predominance of Th1-type cytokines. Clin. Diagn. Lab. Immunol. 5(3), 401–3
Tateda, K., Moore, T. al. (2001). Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. J. Immunol. 166(5), 3355–61
Tilney, L. G., Harb, O. al. (2001). How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough endoplasmic reticulum: implications for conversion of plasma membrane to the endoplasmic reticulum membrane. J. Cell Sci. 114(Pt 24), 4637–50
Ting, J. P. and Williams, K. L. (2005). The CATendoplasmic reticulumPinterleukinLendoplasmic reticulum family: An ancient family of immune/apoptotic proteins. Clin. Immunol. 115(1), 33–7
Vogel, J. P., Andrews, H. al. (1998). Conjugative transfer by the virulence system of Legionella pneumophila. Science 279(5352), 873–6
Weeratna, R., Stamler, D. al. (1994). Human and guinea pig immune responses to Legionella pneumophila protein antigens OmpS and Hsp60. Infect. Immun. 62(8), 3454–62
Wright, E. K., Goodart, S. al. (2003). Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila. Curr. Biol. 13(1), 27–36
Yamamoto, Y., Klein, T. al. (1996). Immunoregulatory role of nitric oxide in Legionella pneumophila-infected macrophages. Cell. Immunol. 171(2), 231–9
Yamamoto, Y., Klein, T. al. (1988). Growth of Legionella pneumophila in thioglycolate-elicited peritoneal macrophages from A/J mice. Infect. Immun. 56(2), 370–5
Yee, R. B. and Wadowsky, R. M. (1982). Multiplication of Legionella pneumophila in unsterilized tap water. Appl. Environ. Microbiol. 43(6), 1330–4