scholarly journals Severe form of Legionnaires' disease in an immunocompetent patient

2009 ◽  
Vol 66 (12) ◽  
pp. 1010-1014
Author(s):  
Ilija Andrijevic ◽  
Jovan Matijasevic ◽  
Djordje Povazan ◽  
Marija Kojicic ◽  
Uros Batranovic
Keyword(s):  
Legionella Pneumophila ◽  
Acute Phase Proteins ◽  
Severe Pneumonia ◽  
Positive Outcome ◽  
Immunocompetent Patient ◽  
Multiple Organ ◽  
Severe Form ◽  
Inflammatory Lesions ◽  
Initial Symptoms ◽  
Legionnaires Disease

Background. Legionnaires' disease (LD) is a pneumonia caused by Legionella pneumophila (LP). The disease occurs more often in immunocompromised persons and can be manifested by severe pneumonia, multiple organ failure and has a high mortality. Case report. Immunocompetent patient, male, 53- year old, with severe form of LB had fever, cough, weakness and diarrhea as the initial symptoms of the disease. Laboratory results showed increased number of leukocytes, increased values of acute phase proteins, liver enzymes and hyponatremia. Computed tomography of the chest showed the marked inflammatory lesions on both sides. Pathohystological analysis of the samples retrieved by bronchoscopy pointed to a pneumonia, and diagnosis of LD was confirmed by positive urine test for LP antigen. Later, the disease was complicated by acute adult respiratory distress syndrome (ARDS). Treatment with antibiotics (erythromycin, rifampicin, azithromycin) combined with ARDS treatment led to a clinical recovery of the patient together with complete resolution of inflammatory lesions seen on chest radiography. Conclusion. In severe pneumonias it is necessary to consider LD in differential diagnosis, perform tests with aim of detecting LP and apply adequate antibiotic treatment in order to accomplish positive outcome of the therapy and prevent complications.

scholarly journals Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

2005 ◽  
Vol 73 (9) ◽  
pp. 5350-5357 ◽  
Author(s):  
Toshiaki Kikuchi ◽  
Sita Andarini ◽  
Hong Xin ◽  
Kazunori Gomi ◽  
Yutaka Tokue ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Host Defense ◽  
Legionella Pneumophila ◽  
Recombinant Adenovirus ◽  
Severe Pneumonia ◽  
Adenovirus Vector ◽  
Recombinant Adenovirus Vector ◽  
Legionnaires Disease

ABSTRACT Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L. pneumophila has not been fully delineated. For this study, we focused on a potent chemoattractant for lymphocytes, fractalkine/CX3CL1, and observed that the fractalkine expression of DCs was somewhat up-regulated when they encountered L. pneumophila. We therefore hypothesized that fractalkine expressed by Legionella-capturing DCs is involved in the induction of T-cell-mediated immune responses against Legionella, which would be enhanced by a genetic modulation of DCs to overexpress fractalkine. In vivo immunization-challenge experiments demonstrated that DCs modified with a recombinant adenovirus vector to overexpress fractalkine (AdFKN) and pulsed with heat-killed Legionella protected immunized mice from a lethal Legionella infection and that the generation of in vivo protective immunity depended on the host lymphocyte subsets, including CD4+ T cells, CD8+ T cells, and B cells. Consistent with this, immunization with AdFKN/Legionella/DC induced significantly higher levels of serum anti-Legionella antibodies of several isotypes than those induced by control immunizations. Further analysis of spleen cells from the immunized mice indicated that the AdFKN/Legionella/DC immunization elicited Th1-dominated immune responses to L. pneumophila. These observations suggest that fractalkine may play an important role in the DC-mediated host defense against intracellular pathogens such as L. pneumophila.

scholarly journals Exploitation of Phosphoinositides by the Intracellular Pathogen, Legionella pneumophila

2020 ◽  
Author(s):  
Colleen M. Pike ◽  
Rebecca R. Noll ◽  
M. Ramona Neunuebel
Keyword(s):  
Membrane Trafficking ◽  
Legionella Pneumophila ◽  
Pathogenic Bacteria ◽  
Severe Pneumonia ◽  
Bacterial Proteins ◽  
Specific Host ◽  
Spatiotemporal Regulation ◽  
Host Membrane ◽  
Membrane Compartments ◽  
Legionnaires Disease

Manipulation of host phosphoinositide lipids has emerged as a key survival strategy utilized by pathogenic bacteria to establish and maintain a replication-permissive compartment within eukaryotic host cells. The human pathogen, Legionella pneumophila, infects and proliferates within the lung’s innate immune cells causing severe pneumonia termed Legionnaires’ disease. This pathogen has evolved strategies to manipulate specific host components to construct its intracellular niche termed the Legionella-containing vacuole (LCV). Paramount to LCV biogenesis and maintenance is the spatiotemporal regulation of phosphoinositides, important eukaryotic lipids involved in cell signaling and membrane trafficking. Through a specialized secretion system, L. pneumophila translocates multiple proteins that target phosphoinositides in order to escape endolysosomal degradation. By specifically binding phosphoinositides, these proteins can anchor to the cytosolic surface of the LCV or onto specific host membrane compartments, to ultimately stimulate or inhibit encounters with host organelles. Here, we describe the bacterial proteins involved in binding and/or altering host phosphoinositide dynamics to support intracellular survival of L. pneumophila.

scholarly journals Reduction of Legionella spp. in Water and in Soil by a Citrus Plant Extract Vapor

2014 ◽  
Vol 80 (19) ◽  
pp. 6031-6036 ◽  
Author(s):  
Katie Laird ◽  
Elena Kurzbach ◽  
Jodie Score ◽  
Jyoti Tejpal ◽  
George Chi Tangyie ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Water System ◽  
Severe Form ◽  
Gas Chromatography Mass Spectrometry ◽  
Free Living ◽  
Content Type ◽  
Soil Systems ◽  
Viable Cells ◽  
Legionnaires Disease ◽  
Soil And Water

ABSTRACTLegionnaires' disease is a severe form of pneumonia caused byLegionellaspp., organisms often isolated from environmental sources, including soil and water.Legionellaspp. are capable of replicating intracellularly within free-living protozoa, and once this has occurred,Legionellais particularly resistant to disinfectants. Citrus essential oil (EO) vapors are effective antimicrobials against a range of microorganisms, with reductions of 5 log cells ml−1on a variety of surfaces. The aim of this investigation was to assess the efficacy of a citrus EO vapor againstLegionellaspp. in water and in soil systems. Reductions of viable cells ofLegionella pneumophila,Legionella longbeachae,Legionella bozemanii, and an intra-amoebal culture ofLegionella pneumophila(water system only) were assessed in soil and in water after exposure to a citrus EO vapor at concentrations ranging from 3.75 mg/liter air to 15g/liter air. Antimicrobial efficacy via different delivery systems (passive and active sintering of the vapor) was determined in water, and gas chromatography-mass spectrometry (GC-MS) analysis of the antimicrobial components (linalool, citral, and β-pinene) was conducted. There was up to a 5-log cells ml−1reduction inLegionellaspp. in soil after exposure to the citrus EO vapors (15 mg/liter air). The most susceptible strain in water wasL. pneumophila, with a 4-log cells ml−1reduction after 24 h via sintering (15 g/liter air). Sintering the vapor through water increased the presence of the antimicrobial components, with a 61% increase of linalool. Therefore, the appropriate method of delivery of an antimicrobial citrus EO vapor may go some way in controllingLegionellaspp. from environmental sources.

scholarly journals Human GBP1 promotes pathogen vacuole rupture and inflammasome activation during Legionella pneumophila infection

2020 ◽  
Author(s):  
Antonia R. Bass ◽  
Sunny Shin
Keyword(s):  
Legionella Pneumophila ◽  
Severe Pneumonia ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Cytokine Release ◽  
Legionnaires Disease ◽  
Cell Cytosol ◽  
Ifn Γ ◽  
Host Cell Cytosol ◽  
Family Cytokine

AbstractThe inflammasome is an essential component of host defense against intracellular bacterial pathogens, such as Legionella pneumophila, the causative agent of the severe pneumonia Legionnaires’ disease. Inflammasome activation leads to recruitment and activation of caspases, which promote IL-1 family cytokine release and pyroptosis. In mice, interferon (IFN) signaling promotes inflammasome responses against L. pneumophila, in part through the functions of a family of IFN-inducible GTPases known as guanylate binding proteins (GBPs) (1). Within murine macrophages, IFN signaling promotes rupture of the L. pneumophila-containing vacuole (LCV), whereas GBPs are dispensable for vacuole rupture. Instead, GBPs facilitate the lysis of cytosol-exposed L. pneumophila. In contrast to mouse GBPs, the functions of human GBPs in inflammasome responses to L. pneumophila are poorly understood. Here, we show that IFN-γ promotes caspase-1, caspase-4, and caspase-5 inflammasome activation during L. pneumophila infection and upregulates GBP expression in primary human macrophages. We find that human GBP1 is important for maximal IFN-γ-driven inflammasome responses to L. pneumophila. Furthermore, IFN-γ signaling promotes the rupture of LCVs. Intriguingly, in contrast to murine GBPs, human GBP1 targets the LCV in a T4SS-dependent manner and promotes vacuolar lysis, resulting in increased bacterial access to the host cell cytosol. Our findings show a key role for human GBP1 in targeting and disrupting pathogen-containing vacuoles and reveal mechanistic differences in how mouse and human GBPs promote inflammasome responses to L. pneumophila.

scholarly journals Functional Type 1 Secretion System Involved in Legionella pneumophila Virulence

2014 ◽  
Vol 197 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Fabien Fuche ◽  
Anne Vianney ◽  
Claire Andrea ◽  
Patricia Doublet ◽  
Christophe Gilbert
Keyword(s):  
Legionella Pneumophila ◽  
Severe Form ◽  
Secretion System ◽  
Host Cells ◽  
Type I ◽  
Secretion Systems ◽  
Content Type ◽  
Legionnaires Disease ◽  
Infectious Cycle

Legionella pneumophilais a Gram-negative pathogen found mainly in water, either in a free-living form or within infected protozoans, where it replicates. This bacterium can also infect humans by inhalation of contaminated aerosols, causing a severe form of pneumonia called legionellosis or Legionnaires' disease. The involvement of type II and IV secretion systems in the virulence ofL. pneumophilais now well documented. Despite bioinformatic studies showing that a type I secretion system (T1SS) could be present in this pathogen, the functionality of this system based on the LssB, LssD, and TolC proteins has never been established. Here, we report the demonstration of the functionality of the T1SS, as well as its role in the infectious cycle ofL. pneumophila. Using deletion mutants and fusion proteins, we demonstrated that therepeats-in-toxin protein RtxA is secreted through an LssB-LssD-TolC-dependent mechanism. Moreover, fluorescence monitoring and confocal microscopy showed that this T1SS is required for entry into the host cell, although it seems dispensable to the intracellular cycle. Together, these results underline the active participation ofL. pneumophila, via its T1SS, in its internalization into host cells.

scholarly journals The Role of Lipids in Legionella-Host Interaction

2021 ◽  
Vol 22 (3) ◽  
pp. 1487
Author(s):  
Bozena Kowalczyk ◽  
Elzbieta Chmiel ◽  
Marta Palusinska-Szysz
Keyword(s):  
Cell Surface ◽  
Legionella Pneumophila ◽  
Cell Envelope ◽  
Severe Pneumonia ◽  
Outer Leaflet ◽  
Host Interaction ◽  
Host Membrane ◽  
Legionnaires Disease ◽  
And Function

Legionella are Gram-stain-negative rods associated with water environments: either natural or man-made systems. The inhalation of aerosols containing Legionella bacteria leads to the development of a severe pneumonia termed Legionnaires’ disease. To establish an infection, these bacteria adapt to growth in the hostile environment of the host through the unusual structures of macromolecules that build the cell surface. The outer membrane of the cell envelope is a lipid bilayer with an asymmetric composition mostly of phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. The major membrane-forming phospholipid of Legionella spp. is phosphatidylcholine (PC)—a typical eukaryotic glycerophospholipid. PC synthesis in Legionella cells occurs via two independent pathways: the N-methylation (Pmt) pathway and the Pcs pathway. The utilisation of exogenous choline by Legionella spp. leads to changes in the composition of lipids and proteins, which influences the physicochemical properties of the cell surface. This phenotypic plasticity of the Legionella cell envelope determines the mode of interaction with the macrophages, which results in a decrease in the production of proinflammatory cytokines and modulates the interaction with antimicrobial peptides and proteins. The surface-exposed O-chain of Legionella pneumophila sg1 LPS consisting of a homopolymer of 5-acetamidino-7-acetamido-8-O-acetyl-3,5,7,9-tetradeoxy-l-glycero-d-galacto-non-2-ulosonic acid is probably the first component in contact with the host cell that anchors the bacteria in the host membrane. Unusual in terms of the structure and function of individual LPS regions, it makes an important contribution to the antigenicity and pathogenicity of Legionella bacteria.

scholarly journals Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires

2015 ◽  
Vol 83 (10) ◽  
pp. 4081-4092 ◽  
Author(s):  
Rebecca E. Wood ◽  
Patrice Newton ◽  
Eleanor A. Latomanski ◽  
Hayley J. Newton
Keyword(s):  
Legionella Pneumophila ◽  
A549 Cells ◽  
Severe Pneumonia ◽  
Rab Gtpase ◽  
Human Pathogens ◽  
Immunofluorescence Analysis ◽  
Content Type ◽  
Extensive Analysis ◽  
Legionnaires Disease ◽  
Environmental Bacteria

Legionellaorganisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed theLegionella-containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis ofLegionella pneumophila. Here, we have characterized theLegionella longbeachaereplicative vacuole (longbeachae-LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV ofL. pneumophila(pneumophila-LCV). We constructed a Dot/Icm-deficient strain by deletingdotBand demonstrated the inability of this mutant to replicate inside THP-1 cells.L. longbeachaedoes not enter THP-1 cells as efficiently asL. pneumophila, and this is reflected in the observation that translocation of BlaM-RalFLLO(where RalFLLOis theL. longbeachaehomologue of RalF) into THP-1 cells by theL. longbeachaeDot/Icm system is less efficient than that byL. pneumophila. This difference is negated in A549 cells whereL. longbeachaeandL. pneumophilainfect with similar entry dynamics. A β-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, theRab-likeeffector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on thelongbeachae-LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to thelongbeachae-LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of theL. longbeachaereplicative vacuole, highlighting phenotypic similarities to the vacuole ofL. pneumophilaas well as unique aspects of LCV biology.

scholarly journals Acute Pneumonia Caused by Clinically Isolated Legionella pneumophila Sg 1, ST 62: Host Responses and Pathologies in Mice

2022 ◽  
Vol 10 (1) ◽  
pp. 179
Author(s):  
Jiří Trousil ◽  
Lucia Frgelecová ◽  
Pavla Kubíčková ◽  
Kristína Řeháková ◽  
Vladimír Drašar ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Lung Infection ◽  
Severe Form ◽  
Host Immunity ◽  
Sequence Type ◽  
Host Responses ◽  
Lung Pathology ◽  
Bacterial Clearance ◽  
Acute Pneumonia ◽  
Legionnaires Disease

Legionnaires’ disease is a severe form of lung infection caused by bacteria belonging to the genus Legionella. The disease severity depends on both host immunity and L. pneumophila virulence. The objective of this study was to describe the pathological spectrum of acute pneumonia caused by a virulent clinical isolate of L. pneumophila serogroup 1, sequence type 62. In A/JOlaHsd mice, we compared two infectious doses, namely, 104 and 106 CFU, and their impact on the mouse status, bacterial clearance, lung pathology, and blood count parameters was studied. Acute pneumonia resembling Legionnaires’ disease has been described in detail.

scholarly journals Molecular Pathogenesis of Infections Caused by Legionella pneumophila

2010 ◽  
Vol 23 (2) ◽  
pp. 274-298 ◽  
Author(s):  
Hayley J. Newton ◽  
Desmond K. Y. Ang ◽  
Ian R. van Driel ◽  
Elizabeth L. Hartland
Keyword(s):  
Endoplasmic Reticulum ◽  
Immune Responses ◽  
Infected Cell ◽  
Legionella Pneumophila ◽  
Severe Form ◽  
Human Infection ◽  
Intracellular Pathogen ◽  
Eukaryotic Proteins ◽  
Acute Pneumonia ◽  
Legionnaires Disease

SUMMARY The genus Legionella contains more than 50 species, of which at least 24 have been associated with human infection. The best-characterized member of the genus, Legionella pneumophila, is the major causative agent of Legionnaires' disease, a severe form of acute pneumonia. L. pneumophila is an intracellular pathogen, and as part of its pathogenesis, the bacteria avoid phagolysosome fusion and replicate within alveolar macrophages and epithelial cells in a vacuole that exhibits many characteristics of the endoplasmic reticulum (ER). The formation of the unusual L. pneumophila vacuole is a feature of its interaction with the host, yet the mechanisms by which the bacteria avoid classical endosome fusion and recruit markers of the ER are incompletely understood. Here we review the factors that contribute to the ability of L. pneumophila to infect and replicate in human cells and amoebae with an emphasis on proteins that are secreted by the bacteria into the Legionella vacuole and/or the host cell. Many of these factors undermine eukaryotic trafficking and signaling pathways by acting as functional and, in some cases, structural mimics of eukaryotic proteins. We discuss the consequences of this mimicry for the biology of the infected cell and also for immune responses to L. pneumophila infection.

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