Cell Biology of Intracellular Infection by Legionella pneumophila PDF

Microbes and Infection 6 (2004) 129–139 www.elsevier.com/locate/micinf Review Cell biology of the intracel...

Microbes and Infection Cell biology of the intracellular infection Maëlle Molmeret a, Dina M. a Department of Microbiology and b Department of Microbiology and c Department of Medical Microbiology d Department of Microbiology and Immunology, Abstract Legionella pneumophila has become a paradigm for replicative niches. The ability to alter host cell mechanism of pathogenesis of Legionnaires’ disease. © 2003 Elsevier SAS. All rights reserved. Keywords: Intracellular; Dot/icm; Secretion 1. Introduction Legionella pneumophila, a Gram-negative bacillus ubiq- uitous in aquatic environments, is responsible for Legion- naires’ disease. It is a facultative intracellular pathogen that can replicate within eukaryotic host cells such as protozoa and macrophages. In humans, L. pneumophila reaches the lungs after inhalation of contaminated aerosol droplets [1,2] (Fig. 1). Once in the lungs, L. pneumophila is ingested by alveolar macrophages, which are the major site of bacterial replication. This results in an acute and severe pneumonia, Legionnaires’ disease. The unique intracellular fate of L. pneumophila the interesting aspects of this organism. Unlike phagosomes containing inert particles or avirulent bacteria, the L. pneumophila-containing vacuoles avoid the “default” en- docytic pathway, recruiting rough endoplasmic reticulum (RER) and mitochondria, to reside in a specialized vacuole allowing intracellular replication [3–7] (Fig. 2). The forma- tion of this specialized vacuole is directed by the type IV secretion system encoded by the dot/icm genes. The dot (defect in organelle trafficking)/icm (intracellular multiplica- tion) loci consist of 23 genes located in two distinct regions of the L. pneumophila chromosome [8–10]. Analysis of the predicted amino acid sequences of the dot/icm genes has revealed several characteristics that indicate a role in conju- * Corresponding author. Tel.: +1-502-852-5351; E-mail address: [email protected] (Y.A. Kwaik). guanosine 3′,5′-bispyrophosphate (ppGpp) through the 130 M. Molmeret et al. / Microbes and Infection 6 (2004) 129–139 within protozoa. (1) L. pneumophila from biofilms with other bacteria, or in suspension, infecting protozoa. (2) Following entry, L. pneumophila resides in a such as the mitochondria and the RER, and does not fuse with lysosomes. (3) Mutants such as dot/icm mutants fuse to lysosomes 3b. L. pneumophila large numbers 3a. (4) The infectious particle is not known, but may include excreted legionella-filled vesicles, intact legionella-filled amoebae, or free legionellae to humans occurs via mechanical means, such as faucets and showerheads. Infection in humans occurs by inhalation of the infectious particle and establishment of escaped their host cell may survive in suspension for long periods of time, reinfect other protozoa, or recolonize biofilms. Reprinted from ASM News. 66 (10) (2000) M. Molmeret et al. / Microbes and Infection 6 (2004) 129–139 131 infection in this amoebae model. L. pneumophila in post-exponential phase becomes cytotoxic by an RpoS- independent pathway. To replicate efficiently in mac- rophages, both RpoS-independent and -dependent mecha- nisms are utilized by L. pneumophila. Thus, when nutrient levels and other conditions are favorable, L. pneu- mophila replicates within host cells, and when amino acids become rare, intracellular bacteria express several traits that permit escape from the host cell, survival in the environment and the transmission to a new host. The relA mutant, producing an undetectable level of ppGpp in the cells during stationary phase, is unable to produce pigment as it becomes flagellated. Although a previ- ous study has shown that RpoS, which accumulates when RelA is activated, is required for intracellular growth in A. castellanii , Zusman et al. have shown that the relA gene product is dispensable for intracellular growth in HL-60-derived human macrophages and in A. castellanii. Moreover, it has also been shown that RelA and RpoS have minor effects on expression of some of the dot/icm genes (icmT, R, Q, P, M, J, F, V, W). Thus, the role of RpoS in the intracellular infection seems to be host cell specific. 3. Adherence and entry into mammalian cells Invasion and intracellular replication of L. pneumophila infection of A. polyphaga within pulmonary cells in the alveoli are the hallmark of Legionnaires’ disease. The alveolar wall is composed of macrophages and type I and type II epithelial cells. The (E and F). Note that in E and from ASM News. 66 attachment of L. pneumophila in macrophages has been shown to be mediated, at least in part, through attachment of complement-coated bacteria to the complement receptor , although non-complement-mediated uptake also occurs [32,33]. The host cell receptor involved in non-complement- mediated uptake in macrophages and epithelial cells is not known. Uptake of L. pneumophila by monocytes and macro- phages has been shown to occur through conventional and coiling phagocytosis [6,32,34–36] (Fig. 2). Since heat-killed and formalin-killed L. pneumophila are also taken up by coiling phagocytosis but are targeted to the lysosomes , this mode of uptake may not play a role in subsequent trafficking of the bacteria. Many clinical isolates of L. pneu- mophila have been shown to be taken up exclusively by conventional phagocytosis [32,34]. In addition, other species of legionellae, such as L. micdadei, which is the second most common species of legionellae that causes Legionnaires’ disease, is taken up exclusively by conventional phagocytosis The bacterial ligand that mediates the coiling mode of phagocytosis is not known. Moreover, the phagocytic recep- tor that binds the bacteria seems to play some role in deter- mining the fate of the intracellular bacteria, since opsoniza- tion with antibodies reduces intracellular growth [31,37,38]. Studies have focused on the genetic aspects of the uptake of L. pneumophila into its host cells. L. pneumophila mutants et al. / Microbes and Infection 6 (2004) 129–139 tion system is ancestrally related to type IV secretion systems that mediate conjugal DNA transfer between bacteria , L. pneumophila may utilize this transporter to transfer macro- molecules into the host cell to evade endocytic fusion [8,10]. The dot/icm loci may be involved in the insertion of a pore in the host cellular membrane through which the effector pro- teins are exported into the host cell [52,53]. The effector molecules involved in intracellular trafficking and evasion of the lysosomal fusion within mammalian cells are cis-acting on the phagosome but do not alter endocytic fusion in the rest of the cell. With few exceptions, the function of indi- vidual Dot/Icm proteins is unknown. The DotA protein was the first to be described. It is a polytopic inner membrane protein with eight hydrophobic transmembrane domains. The dotA mutants are defec- tive in all virulence activities that require the Dot/Icm com- plex [12,45,53,55,57,58]. These data are supported by the fact that the DotA sequence possesses significant similarities to that of TraY [59,60], a component of the type IV trans- porter required for conjugal transfer of plasmids ColIbP9 and R64. However, Nagai and Roy have shown that the DotA protein is also secreted through the Dot/Icm transporter into the culture supernatant during growth of L. pneumophila in liquid broth via a functional type IV secretion system. Electron micrographs also show that purified DotA can form an oligomer [56,61]. As DotH/IcmK and DotO/IcmB in growing L. pneumo- phila cultures are mainly associated with the membranous fraction, and as dot/icm products may be required during direct contact with host cells, the location of DotH and DotO proteins on the surface of L. pneumophila has been examined the. These proteins are surface exposed and associated with a fibrous structure on L. pneumophila after exposure to bone marrow-derived macrophages. In contrast, during broth cul- ture, this fibrous structure is absent. However, using dotA, dotB, dotH, dotO mutants, it has been shown that the exposure of DotO/DotH on the bacterial surface is not depen- dent on other Dot/Icm proteins, including the DotH protein for the DotO exposure, and vice versa. This result shows that the surface exposure of DotH and DotO after contact with macrophages is not dependent on an intact Dot/Icm secretion system. The surface exposure of these two proteins does not involve bacterial contact with the target cell, since bacteria incubated in medium that has been condi- tioned by bone marrow-derived macrophages for 24 h yield almost identical results. In addition, DotH and DotO surface exposure on L. pneumophila requires intracellular growth of the bacteria in macrophages and is observed late in the infection process, mostly when there are more than 30 bacteria per phagosome. In fact, surface-exposed DotH and DotO disappear after uptake but reappear follow- ing intracellular growth. The exposure of these two proteins increases L. pneumophila uptake into cells and may be necessary to promote bacterial escape from the phagosome and to facilitate the initiation of a new infection in macro- phages. These data may also suggest that macrophage et al. / Microbes and Infection 6 (2004) 129–139 133 Using fluorescent markers specific for the ER, it has been shown that the L. pneumophila-containing vacuoles may resemble nascent autophagosomes. Autophagy is a cel- lular process for the degradation of unwanted organelles and cellular components during which the autophagosome is formed from the smooth ER and fuses to lysosomes. The hypothesis that L. pneumophila exploits the autophagy ma- chinery in host cells and establishes an intracellular niche favorable for replication has been challenged recently (see below) [44,64]. Recent studies suggest that fusion or the exchange of lipid bilayer with ER vesicles on the L. pneumophila- containing phagosome occurs, allowing the phagosomal membrane to become as thin as the ER membrane, with similar characteristics [44,64]. It has been shown that, within 5 min of uptake, host vesicles come into contact with wild- type Legionella-containing phagosomes and flatten along the surface of the phagosome, and this process is completed within 15 min and is dot/icm dependent. This is consistent with earlier studies that have shown that after 4 h of infection, there are only a few vesicles associated with the phagosomal membrane, but there are ribosomes studding the phagosomal membrane. In contrast, autophagy takes place within 1 h, and ribosomes, mitochondria, and the nuclear membrane are not attached to the autophagosomal membrane; neither are the tiny hairs that connect ER and L. pneumophila-containing phagosomes. Interestingly, the thickness of the phagosomal membrane becomes similar to that of the ER membrane within 15 min , which doesn’t happen in the autophagy process. Thus, within 15 min of infection, the phagosomal membrane resembles that of the ER. The ribosomes at 6 h stud the phagosomal membrane, and L. pneumophila is thought to be located within the RER on the thickness of the membranes of the ER and the phagosome membranes to provide evidence that L. pneumophila is located within the RER. Immunocytochemical studies should be per- formed to confirm these observations. It is likely that the recruitment of the ER may be involved in the biogenesis of the phagosome that is dependent on the type IV secretion system, since the dot/icm mutants are unable to recruit RER, and their phagosomes fuse to the lysosomes. ht Interestingly, a recent study showed that recruitment of RER to forming-phagosomes may be part of regular phago- cytosis. Electron micrographs of latex beads and patho- gens such as Salmonella within macrophages have shown that ER membranes fuse with plasmalemma, underneath the phagocytic cup, and successive waves of ER are recruited to the phagosomes of latex beads and bacteria. In neutrophils, the bacteria are quickly killed, and the ER is not involved in the turnover of membrane for phagocytosis. However, since the dot/icm system is essential for RER recruitment , it is likely that L. pneumophila utilizes a specific pathogen-regulated process to recruit vesicles, and this pro- cess is distinct from regular phagocytosis. et al. / Microbes and Infection 6 (2004) 129–139 RalF is Fig. 3. The rib mutants’ defect in cytolysis of the host cell is due to a defect in necrosis-mediated killing. Representative transmission electron micro- graphs of infected U937 macrophages at 24 and 48 h post-infection by the wild-type strain AA100 and the GN229 mutant. The original magnifications were 7000× and 5000× for the 24- and 48-h infections, respectively. Reprin- ted from. We have identified five spontaneous mutants that are un- able to egress from the macrophages but are able to grow as well as the wild-type strains within these cells. These mutants, designated rib (release of intracellular bacteria), are defective in the pore-forming toxin/activity as shown by the contact-dependent hemolysis assay and by permeability to propidium iodide upon infection of macrophages and epithe- lial cells. The rib mutants are also defective in acute cytotoxic lethality to A/J mice and fail to cause alveolar inflammation [13,20] indicating a key role for the pore- forming toxin in the pulmonary pathology of the bacterium. We have further documented that the Rib toxin is not re- quired for intracellular trafficking and replication [19–21]. In addition to defects in evasion of lysosomal fusion,. dot/icm mutants are also defective in induction of apoptosis , enhancement of phagocytosis by human-derived mac- rophages and induction of macropinocytic delayed up- take by A/J mouse macrophages. In contrast, rib mutants are defective in pore-forming toxin but are not defective in evasion of lysosomal fusion, intracellular replication, or in- duction of apoptosis [18,20,21]. These observations may suggest that there are at least two pores inserted into host membranes through the type IV secretion system at different stages of the infection. The first pore is the “invasion and trafficking pore”, which is inserted upon initial contact with the host cell to deliver effectors into the host cell cytoplasm and allow the establishment of the intracellular infection. The dot/icm genes necessary for the assembly of the secretion apparatus are constitutively expressed and are required for this step. The second pore is the “egress pore”, which is triggered during the late stages of intracellular replication and is essential for lysis of the host cell (Figs. 3 and 4). This is consistent with the fact that upon transition into the post-exponential growth in vitro, L. pneumophila becomes M. Molmeret et al. / Microbes and Infection 6 (2004) 129–139 135 of mammalian cells by L. pneumophila upon termination of intracellular bacterial replication to egress formation of the mitochondria and RER-surrounded phagosome (A) and during exponential intracellular is turned off, but caspase-3-mediated apoptosis is triggered. Upon transition to the post-exponential is triggered, which results in insertions of pores in the phagosomal membrane first (C), leading to its pores in the plasma membrane (E), leading to osmotic lysis of the cell and release of the intracellular bacteria. Hashemi had observed on electron micrographs that when present in macrophages at numbers greater than 25 per cell, L. pneumophila was usually dispersed within the cyto- plasm of the host cell. to a point 5. Apoptotic or necrotic cell death 86 amino an icmT null 5.1. Induction of apoptosis by L. pneumophila in and pore mammalian but not protozoan host cells expression Apoptosis requires a cascade of activation of a family of cysteine proteases (caspases) that specifically cleave proteins after aspartate residues. Among them, caspase-3 plays a central role, allowing caspase-activated DNase to enter the nucleus and degrade chromosomal DNA. Muller et al. have shown that L. pneumophila induces apoptosis in HL-60 human-derived macrophages after 24–48 h, at a mul- tiplicity of infection (MOI) of 10–100. The induction of apoptosis in mammalian cells is mediated by activation of caspase-3 that is dose dependent and is maximal at 3 h post-infection at an MOI of 50 [16,17] (Fig. 4). In alveolar epithelial cells and macrophages, the induction of apoptosis is dose dependent but not largely growth-phase regulated and can be induced by extracellular bacteria [16,17]. The dot/icm mutants of L. pneumophila are defective in inducing caspase-3 activation and, thus, apoptosis [16,18]. Therefore, the Dot/Icm type IV secretion system of L. pneumophila is essential for the induction of apoptosis in mammalian cells [16,18]. The pore-forming toxin is not required for the induc- tion of apoptosis, but upon entry into the post-exponential growth phase, it enhances the ability of the bacteria to induce apoptosis. Interestingly, L. pneumophila induces apoptosis in human phagocytes but not in protozoan host cells such as A. castel- lanii [19,79]. Moreover, although A. polyphaga is capable of undergoing apoptosis, including DNA fragmentation, upon stimulation by actinomycin D, L. pneumophila does not induce apoptosis in A. polyphaga [17,19]. et al. / Microbes and Infection 6 (2004) 129–139 disruption of organelles and the plasma membrane occurs, culminating in lysis of the host cells and bacterial egress. 5.4. The neuronal apoptosis inhibitory protein (Naip) and susceptibility of mice to L. pneumophila in the L. pneumophila is unable to replicate in macrophages derived from most inbred mouse strains, with the exception of the A/J strain. The natural resistance of these mouse strains to infection with L. pneumophila is controlled by the expression of a single dominant locus mapped on mouse chromosome 13, designated lgn1 [41,43,81]. The intracellu- lar growth of species other than L. pneumophila are not under lgn’s control. The mouse lgn1 region includes six copies of the neuronal apoptosis inhibitory protein (naip) gene. The Naip proteins have been shown to be direct inhibitors of caspases 3 and 7 for pore. Interestingly, the Naip proteins are less expressed in macrophages derived from permissive A/J mice than from the non-permissive inbred strains, but their expression is increased after the phagocytic events in both strains of mice IcmT is. This increase does not require intracellular replication, since the avirulent dotA mutant and the inert latex particles also cause an increase in naip expression. This reduced naip expression in A/J macrophages may result in enhanced ability of L. pneumophila to induce apoptosis through acti- vation of caspase-3 and thus, increased permissiveness to infection. Recently, naip5, also known as birc1e (bacu- loviral inhibitory apoptosis protein repeat-containing 1), was shown to be the only gene responsible for susceptibility to Legionella [85,86]. In contrast to other Naip expression lev- els, Naip5 expression levels have shown large differences between A/J macrophages and non-permissive macrophages. from them is a. A bacterial artificial chromosome (BAC) transgenic line expressing a non-permissive allele of naip5 has exhibited a reduction in permissiveness to Legionella [85,86]. An anti- sense inhibitor of the translation of the mRNA of Naip5 has caused an increase in the permissiveness of permissive and non-permissive macrophages to Legionella. These re- sults indicate a role for birc1e/naip5 in macrophage resis- tance to L. pneumophila infection. The mechanism of action is not yet known. Although Naip differs from the classical IAPs , it was thought to belong to the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins, which were first identified in bacu- loviruses. A recent study has shown that Naip proteins are part of the nucleotide-binding oligomerization domain (NOD) proteins. NOD proteins are a large family of proteins involved in apoptosis and innate immunity [89–91]. Several NOD proteins have already been shown to be implicated in the activation of caspases such as APAF1, which is involved in activation of caspase 9. NOD1 and NOD2, also part of the NOD family, have been shown to mediate the recognition of specific Gram-negative bacterial components such as li- popolysaccharides (LPS) and peptidoglycan, once they are processed in the cytosol [90,93,94]. Most of the NOD family et al. / Microbes and Infection 6 (2004) 129–139 137 protein is not essential in phagosome transport or replicative organelle biogenesis. Interestingly, L. pneumophila avoids phagosome–lysosome fusion within the first few minutes of the intracellular infection, and the phagosomes are converted into endoplasmic reticulum-derived organelles that support intracellular replication. This process involves intercept- ing early secretory vesicles exiting from the transitional ER caspase-3. After 4 h, L. pneumophila starts to replicate within this. The second domain is a central domain, designated replicative organelle. Between 8 and 18 h, the phagosomal membrane is gradually disrupted, and the bacteria become cytoplasmic and are dispersed among cytoplasmic organelles such as mitochondria and lysosomes prior to lysis of the host cell (Molmeret et al., submitted). Further investigations should be focused on determination of whether the disruption of the phagosomal membrane is due to the action of a toxin. Understanding this unique intracellular fate at the molecular and the cellular level will unravel fascinating aspects of the intricate balance in the evolution of this host–parasite inter- action. cascades that References since C.B. Fliermans, Ecology of Legionella: from data to knowledge with y a little wisdom, Microb. Ecol. 32 (1996) 203–228. B.S. Fields, The molecular ecology of legionellae, Trends Microbiol. 4 (1996) 286–290. M.A. Horwitz, S.C. Silverstein, Legionnaires’ disease bacterium (Legionella pneumophila) multiples intracellularly in human mono- cytes, J. Clin. Invest. 66 (1980) 441–450. M.A. Horwitz, The Legionnaires’ disease bacterium (Legionella pneumophila) inhibits phagosome–lysosome fusion in human mono- cytes, J. Exp. Med. 158 (1983) 2108–2126. M.A. Horwitz, Formation of a novel phagosome by the Legionnaires’ disease bacterium (Legionella pneumophila) in human monocytes, J. Exp. Med. 158 (1983) 1319–1331. M.A. Horwitz, Phagocytosis of the Legionnaires’ disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil, Cell 36 (1984) 27–33. M.A. Horwitz, F.R. Maxfield, Legionella pneumophila inhibits acidi- fication of its phagosome in human monocytes, J. Cell Biol. 99 (1984) 1936–1943. G. Segal, M. Purcell, H.A. Shuman, Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila chromosome, Proc. Natl. Acad. Sci. USA 95 (1998) 1669–1674. G. Segal, H.A. Shuman, Intracellular multiplication and human mac- rophage killing by Legionella pneumophila are inhibited by conjugal components of IncQ plasmid RSF1010, Mol. Microbiol. 30 (1998) 197–208. J.P. Vogel, H.L. Andrews, S.K. Wong, R.R. Isberg, Conjugative trans- fer by the virulence system of Legionella pneumophila, Science 279 (1998) 873–876. G. Segal, H.A. Shuman, Legionella pneumophila utilizes the same genes to multiply within Acanthamoeba castellanii and human mac- rophages, Infect. Immun. 67 (1999) 2117–2124. M.S. Swanson, R.R. Isberg, Association of Legionella pneumophila with the macrophage endoplasmic reticulum, Infect. Immun. 63 (1995) 3609–3620. M. Molmeret, O.A. Alli, M. Radulic, M. Susa, M. Doric, Y. Abu Kwaik, The C-terminus of IcmT is essential for pore formation and for intracellular trafficking of Legionella pneumophila within Acan- thamoeba polyphaga, Mol. Microbiol. 43 (2002) 1139–1150. Molmeret et al. / Microbes and Infection 6 (2004) 129–139 D.L. Weinbaum, R.R. Benner, J.N. Dowling, A. Alpern, A.W. Pas- culle, G.R. Donowitz, Interaction of Legionella micdadei with human monocytes, Infect. Immun. 46 (1984) 68–73. J.N. Dowling, A.K. Saha, R.H. Glew, Virulence factors of the family Legionellaceae, Microbiol. Rev. 56 (1992) 32–60. T.W. Nash, D.M. Libby, M.A. Horwitz, Interaction between the legionnaires’ disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone, J. Clin. Invest. 74 (1984) 771–782. M.A. Horwitz, S.C. Silverstein, Interaction of the legionnaires’ disease bacterium (Legionella pneumophila) with human phagocytes II. Anti- by Legionella pneumo- body promotes binding of L. pneumophila to monocytes but does not inhibit intracellular multiplication, J. Exp. Med. 153 (1981) 398–406. S.L. Cirillo, J. Lum, J.D. Cirillo, Identification of novel loci involved in entry by Legionella pneumophila, Microbiology 146 (2000) 1345– is essential for 1359. Infect. Immun. 70 Y. Yamamoto, T.W. Klein, H. Friedman, Genetic control of macroph- age susceptibility to infection by Legionella pneumophila, FEMS Microbiol. Immunol. 89 (1992) 137–146. M.C. Beckers, S. Yoshida, K. Morgan, E. Skamene, P. Gros, Natural resistance to infection with Legionella pneumophila: chromosomal localization of the Lgn1 susceptibility gene, Mamm. Genome 6 (1995) 540–545. M.C. Beckers, E. Ernst, E. Diez, C. Morissette, F. Gervais, K. Hunter, D. Housman, S. Yoshida, E. Skamene, P. Gros, High-resolution link- age map of mouse chromosome 13 in the vicinity of the host resis- tance locus Lgn1, Genomics 39 (1997) 254–263. W.F. Dietrich, D.M. Damron, R.R. Isberg, E.S. Lander, M.S. Swan- son, Lgn1, a gene that determines susceptibility to Legionella pneu- mophila, maps to mouse chromosome 13, Genomics 26 (1995) 443– 450. L.G. Tilney, O.S. Harb, P.S. Connelly, C.G. Robinson, C.R. Roy, How the parasitic bacterium Legionella pneumophila modifies its phago- some and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane, J. Cell Sci. 114 (2001) Infect. Immun. 66 4637–4650. M.S. Swanson, R.R. Isberg, Formation of the Legionella pneumo- phila replicative phagosome, Infect. Agents Dis. 2 (1995) 269–271. J.A. Bozue, W. Johnson, Interaction of Legionella pneumophila with Acanthamoeba catellanii: uptake by coiling phagocytosis and inhibi- tion of phagosome–lysosome fusion, Infect. Immun. 64 (1996) 668– the stationary phase, 673. S. Sturgill-Koszycki, M.S. Swanson, Legionella pneumophila repli- cation vacuoles mature into acidic, endocytic organelles, J. Exp. Med. J. Bacteriol. 192 (2000) 1261–1272. Y. Abu Kwaik, Induced expression of the Legionella pneumophila gene encoding a 20-kilodalton protein during intracellular infection, between Legionella Infect. Immun. 66 (1998) 203–212. L.-Y. Gao, M. Susa, B. Ticac, Y. Abu Kwaik, Heterogeneity in intrac- ellular replication and cytopathogenicity of Legionella pneumophila and Legionella micdadei in mammalian and protozoan cells, Microb. Pathog. 27 (1999) 273–287. L.-Y. Gao, B.J. Stone, J.K. Brieland, Y. Abu Kwaik, Different fates of Legionella pneumophila pmi and mil mutants within human-derived macrophages and alveolar epithelial cells, Microb. Pathog. 25 (1998) 291–306. P.J. Christie, J.P. Vogel, Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells, Trends growth of Legionella Microbiol. 8 (2000) 354–360. J.E. Kirby, R.R. Isberg, Legionnaires’ disease: the pore macrophage and the legion of terror within, Trends Microbiol. 6 (1998) 256–258. J.E. Kirby, J.P. Vogel, H.L. Andrews, R.R. Isberg, Evidence for pore- forming ability by Legionella pneumophila, Mol. Microbiol. 27 (1998) 323–336. J. Coers, C. Monahan, C.R. Roy, Modulation of phagosome biogen- strains and species, Acta esis by Legionella pneumophila creates an organelle permissive for intracellular growth, Nature Cell Biol. 1 (1999) 451–453. Molmeret et al. / Microbes and Infection 6 (2004) 129–139 139 O. Gal-Mor, T. Zusman, G. Segal, Analysis of DNA regulatory ele- Legionella pneumophila ments required for expression of the Legionella pneumophila icm and dot virulence genes, J. Bacteriol. 184 (2002) 3823–3833. P. Anderson, Kinase cascades regulating entry into apoptosis, Micro- biol. Mol. Biol. Rev. 61 (1997) 33–46. M. Enari, H. Sakahira, H. Yokoyama, K. Okawa, A. Iwamatsu, intracellular growth S. Nagata, A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD, Nature 391 (1998) 43–50. A. Muller, J. Hacker, B. Brand, Evidence for apoptosis of human macrophage-like HL-60 cells by Legionella pneumophila infection, Zuckman, Infect. Immun. 64 (1996) 4900–4906. that play distinct S. Hagele, J. Hacker, B.C. Brand, Legionella pneumophila kills for Legionella pneu- human phagocytes but not protozoan host cells by inducing apoptotic 38 (2000) 719–736. cell death, FEMS Microbiol. Lett. 169 (1998) 51–58. J.J. Cohen, Overview: mechanisms of apoptosis, Immunol. Today 14 system of Legionella (1993) 126–130. Y. Yamamoto, T.W. Klein, H. Friedman, Legionella pneumophila growth in macrophages from susceptible mice is genetically con- trolled, Proc. Soc. Exp. Biol. Med. 196 (1991) 405–409. H. Miyamoto, K. Maruta, M. Ogawa, M.C. Beckers, P. Gros, S. Yoshida, Spectrum of Legionella species whose intracellular mul- the Dot/Icm transporter, tiplication in murine macrophages is genetically controlled by Lgn1, Infect. Immun. 64 (1996) 1842–1845. J.K. Maier, Z. Lahoua, N.H. Gendron, R. Fetni, A. Johnston, associated with expo- J. Davoodi, D. Rasper, S. Roy, R.S. Slack, D.W. Nicholson, A.E. MacKenzie, The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7, J. Neurosci. 22 (2002) 2035–2043. E. Diez, Z. Yaraghi, A. MacKenzie, P. Gros, The neuronal apoptosis inhibitory protein (Naip) is expressed in macrophages and is modu- lated after phagocytosis and during intracellular infection with eukaryotic host cells (in Legionella pneumophila, J. Immunol. 164 (2000) 1470–1477. 3971–3982. E.K. Wright, S.A. Goodart, J.D. Growney, V. Hadinoto, M.G. Endrizzi, of Legionella E.M. Long, K. Sadigh, A.L. Abney, I. Bernstein-Hanley, W.F. Dietrich, 158 (2002) 415–419. Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila, Curr. Biol. 13 (2003) 27–36. its participation in E. Diez, S.H. Lee, S. Gauthier, Z. Yaraghi, M. Tremblay, S. Vidal, 40 (2001) 1113– P. Gros, Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila, Nat. Genet. 33 (2003) 55–60. N. Roy, Q.L. Deveraux, R. Takahashi, G.S. Salvesen, J.C. Reed, The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases, EMBO J. 16 (1997) 6914–6925. P. Liston, N. Roy, K. Tamai, C. Lefebvre, S. Baird, G. Cherton-Horvat, R. Farahani, M. McLean, J.E. Ikeda, A. MacKenzie, R.G. Korneluk, Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes, Nature 379 (1996) 349–353. N. Inohara, G. Nunez, The NOD: a signaling module that regulates apoptosis and host defense against pathogens, Oncogene 20 (2001) 6473–6481. M. Desjardins, Endo- N. Inohara, G. Nunez, NODs: intracellular proteins involved in inflammation and apoptosis, Nat. Rev. Immunol. 3 (2003) 371–382. N. Inohara, Y. Ogura, G. Nunez, Nods: a family of cytosolic proteins that regulate the host response to pathogens, Curr. Opin. Microbiol. 5 A bacterial (2002) 76–80. ARF on Legionella Y. Hu, L. Ding, D.M. Spencer, G. Nunez, WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation, J. Biol. vesicular Chem. 273 (1998) 33489–33494. Nat. Cell Biol. 4 (2002) S.E. Girardin, I.G. Boneca, L.A. Carneiro, A. Antignac, M. Jehanno, J. Viala, K. Tedin, M.K. Taha, A. Labigne, U. Zathringer, A.J. Coyle, P.S. DiStefano, J. Bertin, P.J. Sansonetti, D.J. Philpott, Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan, Science 300 (2003) 1584–1587. N. Inohara, Y. Ogura, F.F. Chen, A. Muto, G. Nunez, Human Nod1 confers responsiveness to bacterial lipopolysaccharides, J. Biol. Chem. 276 (2001) 2551–2554. X. Li, G. R. Stark, NFkappaB-dependent signaling pathways, Exp. Hematol. 30 (2002) 285–296.

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