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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Legionella pneumophila is an opportunistic intracellular pathogen that infects macrophages, both in vivo and in vitro. Tetrahydrocannabinol is a major psychoactive component of marijuana and can affect the functional activity of macrophages. In the present study, it was found that the treatment of macrophage cultures from permissive A/J mice with THC enhanced the growth of Legionella in these cells. Legionella grew much better in macrophages treated with low doses of THC, which caused no alteration in the number or viability of macrophages, as compared with growth in untreated cells. Furthermore, lipopolysaccharide-treated A/J mouse macrophages restricted the growth of Legionella, but this growth restriction was overcome by the addition of THC to LPS-treated macrophage cultures after infection. Thus, it is apparent that THC has the ability to enhance the growth of the intracellular opportunistic pathogen Legionella that grows in A/J mouse macrophages.
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PMID:Enhanced growth of Legionella pneumophila in tetrahydrocannabinol-treated macrophages. 130 98

The rapid development of biotechnological methods provides the potential of dissecting the molecular structure of microorganisms. In this review the molecular biology of chlamydia is described. The genus Chlamydia contains three species C. trachomatis, C. psittaci, and C. pneumonia which all are important human pathogens. Chlamydia is obligate intracellular bacteria with a unique biphasic life cycle. The extracellularly chlamydial elementary bodies (EB) are small, metabolic inactive, infectious particles with a tight outer cell membrane. After internalization into host cells the chlamydial structure changes, they transform to reticulated bodies (RB) which become larger, metabolically active, and start to replicate. Fourtysix hrs post infection RB reorganizes to EB followed by burst of the inclusion. The structure of the EB outer membrane differs from the membrane of gram-negative bacteria since it is highly cross-linked by S-S bridges. There are, however, also similarities to gram-negative cell walls. The chlamydial major outer membrane protein, Omp1, forms pores and is closely associated with lipopolysaccharide, LPS. LPS, however, is more loosely associated with Omp1 than in other gram negative bacteria since incubation of EB with antibodies against LPS will liberate it from the chlamydial surface. Therefore the surface localized LPS may be important for chlamydial survival. OMP1 varies between the different serovar of C. trachomatis. Several very conserved regions are separated by variable domains. The variable domains are very antigenic and are localized at the surface of EB. After chlamydial internalization into the host cell transition to RB starts. Some of the early proteins are DnaK-like and groEL-like heat-shock proteins. The chlamydial DnaK-like protein is very antigenic. Patient serum samples will recognize the chlamydial DnaK-like protein. From the determined DNA sequence the amino acid sequence was determined. It was 57% homologous to the Eschrichia coli DnaK protein. Also the GroEL-like protein is antigenic and very conserved. Factors of importance for pathogenicity of chlamydia have not yet been found. The adhesin(s) is unknown, and no factor of importance for the inhibition of fusion between phagosome and host cell lysosomes has been described. A protein similar to the mip gene product of Legionella pneumofila may be a possible candidate for a pathogenicity factor. Diagnosis of C. trachomatis infections has been done by chlamydia cultivation in tissue culture cells, by immunofluorescence and by ELISA. A new method based on the polymerase chain reaction (PCR) has been developed. As primers sequences from the common plasmid were used. This method has high sensitivity and specificity and does not require live chlamydia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The molecular biology and diagnostics of Chlamydia trachomatis. 152 83

Legionella pneumophila is a facultative intracellular bacterial pathogen that parasitizes human monocytes and alveolar macrophages. Previous studies from this laboratory have shown that monocyte complement receptors CR1 and CR3 and complement component C3 in serum mediate L. pneumophila phagocytosis. In this study, we have explored C3 fixation to L. pneumophila. We developed a whole-cell enzyme-linked immunosorbent assay (ELISA) to measure C3 fixation to the bacterial surface. By this assay, C3 fixes to L. pneumophila that are opsonized in fresh nonimmune serum, and C3 fixation takes place via the alternative pathway of complement activation. Immunoblot analysis of opsonized L. pneumophila indicated that C3 fixes selectively to specific acceptor molecules of L. pneumophila. Consistent with this, when nitrocellulose blots of whole L. pneumophila or bacterial components are incubated in fresh nonimmune serum, C3 fixes exclusively to the major outer membrane protein (MOMP) of L. pneumophila, a porin; C3 does not fix to L. pneumophila LPS on these blots. To further explore the role of MOMP in C3 fixation and phagocytosis, we reconstituted purified MOMP into liposomes. By the ELISA, MOMP-liposomes, but not plain liposomes lacking MOMP, avidly fix C3. Consistent with a dominant role for MOMP in C3 fixation, MOMP-liposomes form a C3 complex of the same apparent molecular weight as whole L. pneumophila in nonimmune serum. Opsonized radioiodinated MOMP-liposomes avidly adhere to monocytes, and adherence is dose dependent upon serum. By electron microscopy, opsonized MOMP-liposomes are efficiently phagocytized by human monocytes, and phagocytosis takes place by a conventional appearing form of phagocytosis. This study demonstrates that C3 fixes selectively to the MOMP of L. pneumophila, and that, in the presence of nonimmune serum, MOMP can mediate phagocytosis of liposomes and, potentially, phagocytosis of intact L. pneumophila by human monocytes.
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PMID:Complement component C3 fixes selectively to the major outer membrane protein (MOMP) of Legionella pneumophila and mediates phagocytosis of liposome-MOMP complexes by human monocytes. 221 49

L. pneumophila is a facultative intracellular opportunistic pathogen ubiquitously present in the environment. Much is now known concerning the ecological niche of this organism as well as many other characteristics of these bacteria, including physiology and biochemistry. However, much less is known about immune mechanisms responsible for host resistance vs susceptibility. Not only outer membrane protein rich fractions but also LPS-rich components are potent immunogens, both in experimental animals such as susceptible guinea pigs and more resistant rodent species like rats and mice. Immunity to these organisms can be readily observed by a variety of serologic techniques. Antibody titers increase rapidly after exposure of individuals to these bacteria either by infection or immunization. However, such antibody does not appear to play an important role in host resistance. Serum antibody plus complement is not lytic for the bacteria in vitro. Furthermore, antibody appears to promote the phagocytosis of the bacteria by monocytes and/or macrophages in culture but such phagocytosis does not result in killing of the bacteria, merely an enhanced uptake and subsequent replication of the organisms. Studies on cellular immunity have focused attention on the role of T lymphocytes, monocytes and macrophages. In addition, cutaneous hypersensitivity is readily induced by infection or immunization of experimental animals with Legionella or antigenic components. In vitro correlates of hypersensitivity is also readily evident after infection or immunization. Although lymphoid cells from guinea pigs only show evidence of responsiveness to Legionella antigens by the lymphocyte blastogenic reaction after animals have been sensitized, peripheral blood monocytes from man as well as splenocytes from mice show evidence of responsiveness to Legionella even before known infection or sensitization. However, higher blastogenic responses become evident after sensitization or infection. In addition, interleukins, such as interleukin 1 and 2, as well as interferon and tumor necrotizing factor, appear in response to Legionella antigens and seem to play a role in resistance mechanisms. Cellular replication of Legionella in monocytes from man as well as macrophages from susceptible animals seems related to susceptibility or resistance to these organisms. Further analyses of the nature and mechanism of humoral vs cellular immune responses to Legionella antigens will provide valuable information about immunity and resistance to these intracellular pathogens in susceptible individuals.
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PMID:Legionella pneumophila immunity and immunomodulation: nature and mechanisms. 305 72

Legionella pneumophila, the causative agent of Legionnaires' disease, is a Gram-negative bacterium and a facultative intracellular parasite that multiplies in human monocytes and alveolar macrophages. In this paper, mutants of L. pneumophila avirulent for human monocytes were obtained and extensively characterized. The mutants were obtained by serial passage of wild-type L. pneumophila on suboptimal artificial medium. None of 44 such mutant clones were capable of multiplying in monocytes or exerting a cytopathic effect on monocyte monolayers. Under the same conditions, wild-type L. pneumophila multiplied 2.5-4.5 logs, and destroyed the monocyte monolayers. The basis for the avirulent phenotype was an inability of the mutants to multiply intracellularly. Both mutant and wild-type bacteria bound to and were ingested by monocytes, and both entered by coiling phagocytosis. Thereafter, their intracellular destinies diverged. The wild-type formed a distinctive ribosome-lined replicative phagosome, inhibited phagosome-lysosome fusion, and multiplied intracellularly. The mutant did not form the distinctive phagosome nor inhibit phagosome-lysosome fusion. The mutant survived intracellularly but did not replicate in the phagolysosome. In all other respects studied, the mutant and wild-type bacteria were similar. They had similar ultrastructure and colony morphology; both formed colonies of compact and diffuse type. They had similar structural and secretory protein profiles and LPS profile by PAGE. Both the mutant and wild-type bacteria were completely resistant to human complement in the presence or absence of high titer anti-L. pneumophila antibody. The mutant L. pneumophila have tremendous potential for enhancing our understanding of the intracellular biology of L. pneumophila and other parasites that follow a similar pathway through the mononuclear phagocyte. Such mutants also show promise for enhancing our understanding of immunity to L. pneumophila, and they may serve as prototypes in the development of safe and effective vaccines against intracellular pathogens.
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PMID:Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes. 368 Nov 88

Lipopolysaccharide isolated from Legionella pneumophila was found to be a potent antigen and inducer of antibody with strong adjuvant activity for related and unrelated antigens such as sheep erythrocytes by in vivo and in vitro systems. The LPS was also a potent stimulator of blastogenic responses by spleen cells from normal mice as well as from mice immunized with inactivated whole cells of Legionella. It strongly stimulated production of interferon and interleukin 1. These results indicate that the LPS of Legionella may be an important immune regulator in the host response.
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PMID:Immunogenicity and adjuvanticity of lipopolysaccharide from Legionella pneumophila. 380 73

The lipopolysaccharide (LPS, endotoxin) of Legionella pneumophila serogroup 1 (Philadelphia 1) exhibits peculiar chemical features which may account for its importance as a bacterial virulence factor. The O-chain of this LPS constitutes a homopolymer of an unusual sugar, 5-acetamidino-7-acetamido-8-O-acetyl-3,5,7, 9-tetradeoxy-D-glycero-L-galacto-nonulosonic acid (legionaminic acid) of which about 10-75 residues are present. Due to the lack of free hydroxyl groups, this homopolymer renders the cell surface highly hydrophobic and, therefore, supports adherence to the membrane of target cells including alveolar macrophages. Investigations of the serological specificity of the serogroup 1 LPS revealed a monoclonal antibody (mAb 3/1) which recognizes an epitope located in the environment of the 8-O-acetyl group of legionaminic acid. According to epidemiological studies, this determinant appears to be associated with L. pneumophila virulence. The outer core oligosaccharide of L. pneumophila LPS exhibits also hydrophobic properties due to the presence of N- and O-acetyl groups as well as 6-deoxy sugars. The inner core expresses both similarities and differences as compared to enterobacterial core oligosaccharides in containing Kdo but lacking heptose and phosphate groups. Lipid A possesses some unique structural features since its backbone consists of a bisphosphorylated beta-GlcpN3N-(1-->6)-GlcpN3N disaccharide with only amide-linked acyl groups having 14-22 carbon atoms. Long chain fatty acids [28:0(27-oxo) and 27:0-dioic] possessing the double length as enterobacterial acyl groups, may be responsible for the low endotoxicity of L. pneumophila lipid A.
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PMID:The lipopolysaccharide of Legionella pneumophila serogroup 1 (strain Philadelphia 1): chemical structure and biological significance. 852 18

A highly sensitive latex test system for identification of Legionella in the external medium and clinical materials have been designed. Protein antigens and polysaccharide components of the outer membrane of the agent were analyzed. Proteins having a molecular mass of 45, 29, and 24 kDa, as well as a polysaccharide component of LPS were found to be common for all L. pneumophila species. Highly affinic immunoglobulins to the antigenic components obtained were covalently linked with latex particles. The test system developed does not give cross-reactions with other microorganisms. The sensitivity of the system is 10(4) COE/ml. Testing water and clinical material samples confirmed that the developed system is more sensitive than the bacteriological method and the direct fluorescence test. In addition, the system is simple to use, cost-effective, it requires little time (no more than 5 min).
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PMID:[Designing the latex test system for express identification of legionella in the external medium and clinical materials]. 928 79

The ability of Legionella species to multiply within human mononuclear phagocytes is usually regarded as being associated with their pathogenicity. Activation of host cells results in inhibition of intracellular Legionella multiplication. The most effective substance to induce macrophage activation, both in vivo and in vitro, is interferon-gamma. In addition, some evidence exists that macrophage-derived cytokines may contribute to the host defense against L. pneumophila, but the production of pro- and antiinflammatory cytokines by monocytes after infection with different Legionella species has not been reported with regard to their ability to multiply within the host cells. We therefore examined the production of TNF-alpha, IL-1, IL-6, IL-8, IL-10 and TGF-beta by Mono Mac 6 cells after infection with Legionella species of different human prevalence that differ in their ability to replicate within this macrophage-like cell line. After infection, Mono Mac 6 cells showed a cytokine response with time kinetics characteristic for the cytokine. Maximum cytokine levels produced differed with Legionella species, but were not related to intracellular multiplication rates. Moreover, LPS-tolerant Mono Mac 6 cells, which failed to produce cytokines, showed intracellular increase or decrease of bacterial numbers identical to that of untreated Mono Mac 6 cells. By FACS analysis, an up-regulation of CD14 (LPS receptor) and CD54 (ICAM-1) could be demonstrated. We conclude that, in the Mono Mac 6 cell line, induction of macrophage-derived cytokines after infection with members of the genus Legionella mimics an inflammatory reaction without association with intracellular multiplication rate.
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PMID:Induction of cytokines and expression of surface receptors in Mono Mac 6 cells after infection with different Legionella species. 953 66

Legionella pneumophila, a gram-negative bacterium causing Legionnaires' disease and Pontiac fever, was shown to be highly reactive in in vitro gelation of Limulus lysate but not able to induce fever and the local Shwartzman reaction in rabbits and mice. We analyzed the capacity of purified L. pneumophila lipopolysaccharide (LPS-Lp) to induce activation of the human monocytic cell line Mono Mac 6, as revealed by secretion of proinflammatory cytokines and desensitization to subsequent LPS stimulation. We showed that despite normal reactivity of LPS-Lp in the Limulus amoebocyte lysate assay, induction of cytokine secretion in Mono Mac 6 cells and desensitization to an endotoxin challenge required LPS-Lp concentrations 1,000 times higher than for LPS of Salmonella enterica serovar Minnesota. Therefore, we examined the interaction of LPS-Lp with the LPS receptor CD14. We demonstrated that LPS-Lp did not bind to membrane-bound CD14 expressed on transfected CHO cells, nor did it react with soluble CD14. Our results suggest that the low endotoxic potential of LPS-Lp is due to a failure of interaction with the LPS receptor CD14.
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PMID:Low endotoxic potential of Legionella pneumophila lipopolysaccharide due to failure of interaction with the monocyte lipopolysaccharide receptor CD14. 971 61


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