Cutting Edge: Pulmonary<i>Legionella pneumophila</i>Is Controlled by Plasmacytoid Dendritic Cells but Not Type I IFN

Ang, Desmond Ky; Oates, Clare V.; Schuelein, Ralf; Kelly, Michelle L.; Sansom, Fiona M.; Bourges, Dorothée; Boon, Louis; Hertzog, Paul J.; Hartland, Elizabeth L.; Driel, Ian R. van

doi:10.4049/jimmunol.1000128

Cited by 43 publications

(38 citation statements)

References 36 publications

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“…Furthermore, type I IFN-␣ receptor-deficient (IFNAR Ϫ/Ϫ ) macrophages were more permissive to L. pneumophila infection in vitro than were wild-type cells (11). There was no difference in bacterial detection in the lungs when IFNAR2 Ϫ/Ϫ and wild-type mice were compared 48 h after L. pneumophila infection (12), nor was there a difference in lung bacterial burden between wild-type and IFNAR Ϫ/Ϫ mice (13). Despite this, most reports suggest that type I IFN supports cellular resistance to L. pneumophila infection.…”

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confidence: 91%

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

et al. 2016

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Coxiella burnetii is an intracellular pathogen and the cause of Q fever. Gamma interferon (IFN-␥) is critical for host protection from infection, but a role for type I IFN in C. burnetii infection has not been determined. Type I IFN supports host protection from a related pathogen, Legionella pneumophila, and we hypothesized that it would be similarly protective in C. burnetii infection. In contrast to our prediction, IFN-␣ receptor-deficient (IFNAR ؊/؊ ) mice were protected from C. burnetii-induced infection. Therefore, the role of type I IFN in C. burnetii infection was distinct from that in L. pneumophila. Mice treated with a double-stranded-RNA mimetic were protected from C. burnetii-induced weight loss through an IFNAR-independent pathway. We next treated mice with recombinant IFN-␣ (rIFN-␣). When rIFN-␣ was injected by the intraperitoneal route during infection, disease-induced weight loss was exacerbated. Mice that received rIFN-␣ by this route had dampened interleukin 1␤ (IL-1␤) expression in bronchoalveolar lavage fluids. However, when rIFN-␣ was delivered to the lung, bacterial replication was decreased in all tissues. Thus, the presence of type I IFN in the lung protected from infection, but when delivered to the periphery, type I IFN enhanced disease, potentially by dampening inflammatory cytokines. To better characterize the capacity for type I IFN induction by C. burnetii, we assessed expression of IFN-␤ transcripts by human macrophages following stimulation with lipopolysaccharide (LPS) from C. burnetii. Understanding innate responses in C. burnetii infection will support the discovery of novel therapies that may be alternative or complementary to the current antibiotic treatment.

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confidence: 91%

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

et al. 2016

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“…Whether L. pneumophila can survive within neutrophils and translocate T4SS effectors into these cells during pulmonary infection is unknown. L. pneumophila can be taken up by a wide variety of cell types in vitro, such as neutrophils, bone marrow-derived dendritic cells, type I and type II alveolar epithelial cells, endothelial cells, and plasmacytoid dendritic cells (35)(36)(37)(38)(39). However, the efficiency of L. pneumophila replication within these cell types varies greatly, and whether these cell types are injected by the T4SS or productively infected in vivo is unknown.…”

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confidence: 99%

Alveolar Macrophages and Neutrophils Are the Primary Reservoirs for Legionella pneumophila and Mediate Cytosolic Surveillance of Type IV Secretion

et al. 2014

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c Legionella pneumophila, an intracellular pathogen responsible for the severe pneumonia Legionnaires' disease, uses its dot/icmencoded type IV secretion system (T4SS) to translocate effector proteins that promote its survival and replication into the host cell cytosol. However, by introducing bacterial products into the host cytosol, L. pneumophila also activates cytosolic immunosurveillance pathways, thereby triggering robust proinflammatory responses that mediate the control of infection. Thus, the pulmonary cell types that L. pneumophila infects not only may act as an intracellular niche that facilitates its pathogenesis but also may contribute to the immune response against L. pneumophila. The identity of these host cells remains poorly understood. Here, we developed a strain of L. pneumophila producing a fusion protein consisting of ␤-lactamase fused to the T4SS-translocated effector RalF, which allowed us to track cells injected by the T4SS. Our data reveal that alveolar macrophages and neutrophils both are the primary recipients of T4SS-translocated effectors and harbor viable L. pneumophila during pulmonary infection of mice. Moreover, both alveolar macrophages and neutrophils from infected mice produced tumor necrosis factor and interleukin-1␣ in response to T4SS-sufficient, but not T4SS-deficient, L. pneumophila. Collectively, our data suggest that alveolar macrophages and neutrophils are both an intracellular reservoir for L. pneumophila and a source of proinflammatory cytokines that contribute to the host immune response against L. pneumophila during pulmonary infection.

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“…Similarly to macrophages, dendritic cells (including plasmocytoid dendritic cells) are recruited in the early stages of Legionella infection in mice [9]. Although able to phagocytose Legionella, in vivo infections in mice have demonstrated that dendritic cells contain only a few bacteria at a time.…”

Section: Legionella Infection In Other Immune Cellsmentioning

confidence: 99%

“…Within the lungs, Legionella are phagocytosed by resident alveolar macrophages [8] and, in mice, by recruited dendritic cells [9]. Macrophages are specialized phagocytes capable of engulfing whole cells destined for destruction within hydrolytic lysosomes, called phagolysosomes.…”

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confidence: 99%

Programmed Cell Death in Legionella Infection

2013

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The causative agent of Legionnaires' disease, Legionella pneumophila, resides within alveolar macrophages by exporting 295 bacterial virulence proteins (effectors) to modulate host cell processes. This leads to the formation of a unique vacuolar niche and the suppression of macrophage cell death pathways, which, in turn, promote bacterial survival and allow sufficient time for replication. However, once nutrients within the vacuole are depleted, Legionella must act to induce host cell death in order to facilitate bacterial egress and reinfect new cells. Intracellular Legionella also evade detection by the host cell's innate immune system, which seeks to destroy invading pathogens by activating inflammasome complexes, thereby promoting proinflammatory cytokine activation and pyroptotic cell death. Understanding how different forms of programmed cell death contribute to Legionella infectivity and are manipulated by Legionella effector proteins will be important for identifying novel antibacterial therapeutic targets.

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Cutting Edge: PulmonaryLegionella pneumophilaIs Controlled by Plasmacytoid Dendritic Cells but Not Type I IFN

Cited by 43 publications

References 36 publications

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

Alveolar Macrophages and Neutrophils Are the Primary Reservoirs for Legionella pneumophila and Mediate Cytosolic Surveillance of Type IV Secretion

Programmed Cell Death in Legionella Infection

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