Pneumonitis Caused by Legionella pneumoniae in a Patient With Rheumatoid Arthritis Treated With Anti-TNF-?? Therapy (Infliximab)

F, Li Gobbi; Benucci, Maurizio; A, Del Rosso

doi:10.1097/01.rhu.0000158527.20518.30

Cited by 24 publications

(11 citation statements)

References 9 publications

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“…In this study, we showed that host cells have evolved mechanisms to cope with translation inhibition by selectively translating a subset of cytokine genes, including pro-inflammatory cytokines such as IL-1α and IL-1β in response to L. pneumophila challenge. The ability to bypass L. pneumophila translational inhibition is an important determinant of host protection, as mice defective in the IL-1α/IL-1β response and humans exposed to TNF-α inhibitors are highly susceptible to L. pneumophila infection [31], [38].…”

Section: Discussionmentioning

confidence: 99%

“…The importance of cytokines can be seen in IL-1α, IL-12, IFN-γ and TNF knockout mouse strains that show increased susceptibility to L. pneumophila infection [31], [37]. Moreover, patients treated with TNF-α blockers are at high risk of developing severe Legionnaires' disease [38]. Given the key role that this innate immune response plays in clearance of L. pneumophila , we examined how cytokines and other immune mediators are synthesized under conditions in which the bacterium effectively blocks the host protein translation machinery.…”

Section: Introductionmentioning

confidence: 99%

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The Frustrated Host Response to Legionella pneumophila Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines

2014

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Many pathogens, particularly those that require their host for survival, have devised mechanisms to subvert the host immune response in order to survive and replicate intracellularly. Legionella pneumophila, the causative agent of Legionnaires' disease, promotes intracellular growth by translocating proteins into its host cytosol through its type IV protein secretion machinery. At least 5 of the bacterial translocated effectors interfere with the function of host cell elongation factors, blocking translation and causing the induction of a unique host cell transcriptional profile. In addition, L. pneumophila also interferes with translation initiation, by preventing cap-dependent translation in host cells. We demonstrate here that protein translation inhibition by L. pneumophila leads to a frustrated host MAP kinase response, where genes involved in the pathway are transcribed but fail to be translated due to the bacterium-induced protein synthesis inhibition. Surprisingly, few pro-inflammatory cytokines, such as IL-1α and IL-1β, bypass this inhibition and get synthesized in the presence of Legionella effectors. We show that the selective synthesis of these genes requires MyD88 signaling and takes place in both infected cells that harbor bacteria and neighboring bystander cells. Our findings offer a perspective of how host cells are able to cope with pathogen-encoded activities that disrupt normal cellular process and initiate a successful inflammatory response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Frustrated Host Response to Legionella pneumophila Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines

2014

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“…Legionella pneumonia has been reported in patients with RA, particularly those receiving TNF-I therapy (11)(12)(13)(14). According to the French registry, the relative risk of Legionellosis was estimated at 16.5-21 for patients with chronic inflammatory diseases receiving TNF-I therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Legionella pneumonia, an opportunistic infection, has been reported in patients treated with TNF-I (11)(12)(13)(14) but not with TCZ. We herein report an RA patient who developed severe pneumonia caused by Legionella pneumophila under treatment with TCZ.…”

Section: Introductionmentioning

confidence: 99%

Fatal Complication of <i>Legionella pneumophila</i> Pneumonia in a Tocilizumab-treated Rheumatoid Arthritis Patient

et al. 2015

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We herein report a fatal case of Legionella pneumophila pneumonia in a tocilizumab-treated rheumatoid arthritis patient who was in a state of shock on admission but remained afebrile even during severe pneumonia. Legionella antigen was detected in the urine and neutrophil CD64 expression was highly elevated. Despite undergoing intensive treatment, the patient developed sepsis and died 12 days after admission. An autopsy indicated that while the Legionella infection had almost been controlled, a subarachnoid hemorrhage was the ultimate cause of death.

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“…Les quelques données de travaux in vitro supportent une relation entre l'abus de cocaïne, l'utilisation de marijuana et les infections à légionelle. Des données de la littérature ont impliqué les traitements par anti-TNF (Tumor Necrosis Factor) alpha (infliximab) dans les légionelloses [12]. Cependant, des cas sévères de légionellose sont diagnostiqués chez des patients n'ayant aucun facteur de risque et l'absence de ces facteurs ne doit pas exclure le diagnostic de légionellose.…”

Section: Susceptibilité Individuelleunclassified

Légionellose

et al. 2007

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Legionnaires disease, more formally known as legionellosis, is a relatively common form of severe pneumonia caused by Legionella, a genus of waterborne bacteria. Legionellosis is acquired by inhalation of legionellae from contaminated environmental sources. Legionella pneumophila serogroup 1 is responsible for more than 80% of cases in most countries. More than 1500 cases were reported in France in 2005. Initial diagnosis is based on tests for urinary antigens. The mortality rate for legionellosis depends on the promptness of appropriate antibiotic therapy. Macrolides (erythromycin or intravenous azithromycin, which is preferred to erythromycin for its better pharmacodynamic properties) and fluoroquinolones (levofloxacin) are the antibiotics of choice for severe legionellosis.

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Pneumonitis Caused by Legionella pneumoniae in a Patient With Rheumatoid Arthritis Treated With Anti-TNF-?? Therapy (Infliximab)

Cited by 24 publications

References 9 publications

The Frustrated Host Response to Legionella pneumophila Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines

The Frustrated Host Response to Legionella pneumophila Is Bypassed by MyD88-Dependent Translation of Pro-inflammatory Cytokines

Fatal Complication of <i>Legionella pneumophila</i> Pneumonia in a Tocilizumab-treated Rheumatoid Arthritis Patient

Légionellose

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