Innate immune responses and monocyte-derived phagocyte recruitment in protective immunity to pathogenic bacteria: insights from Legionella pneumophila.

Legionella species are Gram-negative intracellular bacteria that evolved in soil and freshwater environments, where they infect and replicate within various unicellular protozoa. The primary virulence factor of Legionella is the expression of a type IV secretion system (T4SS), which contributes to the translocation of effector proteins that subvert biological processes of the host cells. Because of its evolution in unicellular organisms, T4SS effector proteins are not adapted to subvert specific mammalian signaling pathways and immunity. Consequently, Legionella pneumophila has emerged as an interesting infection model for investigating immune responses against pathogenic bacteria in multicellular organisms. This review highlights recent advances in our understanding of mammalian innate immunity derived from studies involving L. pneumophila. This includes recent insights into inflammasome-mediated mechanisms restricting bacterial replication in macrophages, mechanisms inducing cell death in response to infection, induction of effector-triggered immunity, activation of specific pulmonary cell types in mammalian lungs, and the protective role of recruiting monocyte-derived cells to infected lungs.

A Novel Case of Legionnaire's Disease after Staying at Home Rentals.

Case of a 44-year-old woman with past medical history of dermatomyositis who had been on Methrotexate therapy who became infected with Legionella pneumophila after staying at a home rental, known commercially as an Airbnb. The patient presented to the ER with complaints of general malaise and subsequently developed sepsis with respiratory failure requiring intubation. CT scan confirmed the diagnosis of pneumonia and through extensive research L. pneumophila was identified using a pneumonia panel that works by identifying nucleic acids of fastidious organisms that are difficult and take long to grow by culture. As the patient's pneumonia progressed to ARDS and her clinical impression worsened, pronation technique was begun in addition to her course of antibiotics that were already being administered. The patient began showing significant improvement in her clinical picture and was extubated with progressive recovery.

[Legionnaires' disease in Argentina: Evolution of the laboratory diagnostic strategy]. / Enfermedad del legionario en Argentina: evolución de la estrategia diagnóstica en el laboratorio.

Legionnaires' disease (LD) is severe acute pneumonia that occurs in sporadic or epidemic form, and generally requires hospitalization. The objective of this work was to describe the experience in the LD laboratory diagnostic approach in Argentina during the period 2016-2021. The laboratory analyzed 168 clinical specimens from 93 cases of suspected LD pneumonia. Laboratory tests included the detection of the soluble antigen of Legionella pneumophila serogroup 1 in urine sample, detection of DNA of Legionella spp. in lower respiratory secretions by conventional and commercial molecular methods and isolation in selective medium. LD was confirmed in 12 patients. The urinary antigen allowed the diagnosis for 8 patients. L. pneumophila was isolated from the respiratory material of 6 patients suffering from health care-associated pneumonia, who had been previously diagnosed using the commercial molecular method. Fifty percent of these cases did not show detectable urinary antigen. A single patient did not shows neither detectable antigenuria nor isolation of Legionella from the respiratory sample and was diagnosed as a confirmed case of LD by the detection of DNA of Legionella spp. by PCR directly from the respiratory secretion and the epidemiological link with another case of confirmed LD by culture. Urinary antigen detection is the first-line diagnostic test. However, the incorporation of complementary molecular methods has proved to avoid false negatives and contributed to a better understanding of the true incidence of the disease.

Inflammasome activation and CCR2-mediated monocyte-derived dendritic cell recruitment restrict Legionella pneumophila infection.

Flagellin-induced NAIP/NLRC4 inflammasome activation and pyroptosis are critical events restricting Legionella pneumophila infection. However, the cellular and molecular dynamics of the in vivo responses against this bacterium are still unclear. We have found temporal coordination of two independent innate immunity pathways in controlling Legionella infection, the inflammasome activation and the CCR2-mediated Mo-DC recruitment. Inflammasome activation was an important player at the early stage of infection by lowering the numbers of bacteria for an efficient bacterial clearance conferred by the Mo-DC at the late stage of the infection. Mo-DC emergence highly depended on CCR2-signaling and dispensed inflammasome activation and pyroptosis. Also, Mo-DC compartment did not rely on the inflammasome machinery to deliver proper immune responses and was the most abundant cytokine-producing among the monocyte-derived cells in the infected lung. Importantly, when the CCR2- and NLRC4-dependent axes of response were simultaneously ablated, we observed an aggravated bacterial burden in the lung of infected mice. Taken together, we showed that inflammasome activation and CCR2-mediated immune response interplay in distinct pathways to restrict pulmonary bacterial infection. These findings extend our understanding of the in vivo integration and cooperation of different innate immunity arms in controlling infectious agents.

Probable caso de reinfección grave por SARS-CoV-2 con coinfección por Legionella pneumophila / Probable case of severe SARS-CoV-2 reinfection with Legionella pneumophila co-infection

Resumen La inmunidad conferida luego de una primera infección por SARS-CoV-2 y el riesgo consiguiente de infección persistente o reinfección no están completamente dilucidados. Existen reportes internacionales de casos de reinfección, incluyendo el primer caso publicado en Sudamérica. Por otra parte, las comunicaciones de casos de coinfecciones han ido en aumento, incluyendo las asociadas a Legionella pneumophila . Presentamos el caso de un varón de 47 años de edad, personal de salud, que luego de cuatro meses de una primera infección por SARS-CoV-2, presenta una neumonía grave, certificándose una nueva infección por SARS-CoV-2 y una coinfección por L. pneumophila mediante detección de antígeno urinario. Fue tratado en UCI, requiriendo ventilación mecánica, dexametaxona y moxifloxacino, con buena respuesta clínica. Actualmente se encuentra en rehabilitación respiratoria y motora.

Abstract The immunity conferred after a first SARS-CoV-2 infection and the consequent risk of persistent infection or reinfection are not fully elucidated. There are reports both in Europe and in North America of reinfection cases, recently highlighting the first case published in South America. On the other hand, reports of co-infections have been increasing, including those associated with Legionella pneumophila . We present the case of a 47-year-old male, health personnel who, after four months of a first SARS-CoV-2 infection, suffers a severe pneumonia certifying a new SARS-CoV-2 infection and a L. pneumophila co-infection by urinary antigen detection. He was treated in the ICU, requiring mechanical ventilation, dexamethasone, and moxifloxacin, with a good response. He is currently in respiratory and motor rehabilitation.

Legionella pneumophila: un patógeno emergente en Argentina / Legionella pneumophila: an emerging pathogen in Argentina

La enfermedad del Legionario es causada por bacterias pertenecientes al género Legionella, siendo la especie pneumophila el principal agente etiológico de esta patología. Esta bacteria se describió por primera vez en 1977 como causa de un brote de neumonía grave registrado en 1976 en un centro de convenciones en los Estados Unidos de América. La enfermedad se presenta como una neumonía atípica, responsable del 1 al 15 % de los casos de neumonías adquiridas en la comunidad (NAC), del 5 al 10% de neumonías del adulto y del 1% en menores de 15 años. Los miembros de la familia Legionellaceae son bacilos aeróbicos gramnegativos que crecen lentamente y se encuentran ampliamente distribuidos en cuerpos de agua. La forma más común de transmisión de Legionella spp es la inhalación de aerosoles contaminados generados a partir de fuentes de agua artificiales. Se asocian con la aparición de brotes esporádicos y epidémicos en la comunidad y en infecciones nosocomiales. Las especies pertenecientes al género Legionella se consideran patógenos emergentes transmitidos por el agua. El objetivo de este trabajo es realizar una revisión sobre las manifestaciones y presentaciones clínicas de la infección causada por L. pneumophila, en virtud de que es considerado mundialmente un patógeno emergente y por existir evidencias de su presencia en sistemas de almacenamiento de agua tratada en la región nordeste de la República Argentina, razón primordial para alertar y actualizar conocimientos al respecto

Legionnaires' disease is caused by bacteria belonging to the genus Legionella, being the pneumophila specie the main etiological agent of this pathology. This bacterium was first described in 1977 as the cause of a severe pneumonia outbreak in 1976 at a convention center in the United States of America. The disease presents as an atypical pneumonia, responsible for 1% to 15% of cases of community-acquired pneumonia (CAP), 5% to 10% of pneumonia in adults and 1% in children under 15 years of age. Members of the Legionellaceae family are aerobic, gram-negative rods that grow slowly and are widely distributed in water bodies. The most common way of transmission of Legionella spp is the inhalation of contaminated aerosols generated from artificial water sources. They are associated with the appearance of sporadic and epidemic outbreaks in the community and in nosocomial infections. Species belonging to the genus Legionella are considered emerging waterborne pathogens.The aim of this work is to carry out a review on the manifestations and clinical presentations of the infection caused by L. pneumophila, due to that it is considered an emerging pathogen worldwide and because there is evidence of its presence in storage systems of treated water in the Northeast region of the Argentine Republic, primary reason to alert and update knowledge in this regard.

Identificação molecular de amostras de Legionella pneumophila provenientes de fontes ambientais / Molecular identification of samples of Legionella pneumophila from environmental sources

Legionella pneumophila (Lp) é uma bactéria Gram negativa encontrada em ambientes aquáticos naturais e artificiais nos quais a inalação de aerossóis contaminados pode causar uma pneumonia severa conhecida como Doença dos Legionários com taxa de mortalidade de 10% em indivíduos saudáveis. No Brasil há poucas informações a respeito deste patógeno, mas sabe se que a Pneumonia Adquirida na Comunidade foi responsável por 598.668 hospitalizações e 52.776 mortes só no ano de 2017 e acredita-se que uma porcentagem significativa desses casos seja causada pela Lp. Além disso, os casos de legioneloses vêm crescendo ao redor do mundo e um dos fatores associados a isto é o aumento de sistemas artificiais de água e da exposição humana a fontes contaminadas. A única forma de prevenir a doença dos legionários é pelo controle e tratamento destes ambientes artificiais, especialmente aqueles em grandes edifícios. Sendo assim, o objetivo deste estudo foi caracterizar amostras de Legionella spp. provenientes de fontes ambientais previamente identificadas pela Conforlab. O estudo contou com 50 amostras de Legionella spp. isoladas em meio BCYE a partir de diversas fontes ambientais em nove estados brasileiros fornecidas pela empresa Conforlab. A identificação molecular das amostras foi realizada pela técnica Sequence-based Typing que consiste no sequenciamento e análise de sete genes para a obtenção de um Sequence Type (ST)As amostras foram obtidas de amostras provenientes de hotéis, centros comerciais, laboratórios, empresa e indústria. Cerca de 70% das amostras são da região sudeste do país e 50% do estado de São Paulo. Foram identificados 11 STs entre 34 amostras, dos quais oito são previamente descritos e três STs novos (ST2960, ST2962 e ST2963). Dois complexos clonais foram identificados CC-ST1 e CC-ST1642. O novo ST2960 foi identificado em quatro diferentes torres de resfriamento. O sequenciamento genômico foi realizado em duas amostras de Legionella spp. no qual a sequência da amostra 20935 corresponde a espécie Lp enquanto o outro genoma apresentou maior similaridade com a espécie Legionella anisa, sendo essa a segunda espécie do gênero mais encontrada em amostras de água. Como esperado ST1 foi prevalente, pois é amplamente distribuído na maioria dos países, e os outros STs previamente descritos estão associados às legioneloses em outros países. Dado o grande número de casos de pneumonia anualmente, estima-se que ocorra no Brasil cerca de seis mil óbitos por ano devido à doença dos legionários. Portanto, é necessário que medidas de vigilância e controle da presença de Legionella spp. sejam implementadas, além da realização de mais estudos para a maior compreensão deste patógeno no país. (AU)

Evaluación de la viabilidad de Legionella pneumophila en muestras de agua / Evaluation of the viability of Legionella pneumophila in water samples

Introducción: Legionella pneumophila se sitúa entre los principales agentes causales de neumonía adquirida en la comunidad y de origen nosocomial. La inhalación de aerosoles potencialmente contaminados con la bacteria, producto de la colonización de redes y otros sistemas que utilizan agua, representa un peligro para la salud de los individuos expuestos. Objetivo: evaluar la viabilidad de L. pneumophila en muestras de agua almacenadas en diferentes intervalos de tiempo para el diagnóstico por cultivo microbiológico de Legionella spp. Métodos: Se contaminaron artificialmente muestras de agua con dos cepas de L. pneumophila de serogrupos diferentes y la conformación de una mezcla de ellas, para un total de 15 muestras. Los frascos contaminados fueron procesados a las 24 h, 72 h, 7 días, 14 días y 21 días. Se realizó cultivo microbiológico según ISO 11731: 2004 y PNO 03-013: 2015. Resultados: Se demostró viabilidad de la bacteria en muestras almacenadas hasta 21 días. El método de concentración por filtración resultó tener los mayores recobrados del microorganismo. Conclusiones: El tiempo de almacenamiento de las muestras afecta la viabilidad de L. pneumophila. Sienta las bases para estudios posteriores de robustez del diagnóstico de L. pneumophila como parte del servicio que presta el Centro de Investigaciones Científicas de la Defensa Civil en los programas de prevención y control Legionella spp. en instalaciones de interés turístico e industrial(AU)

Introduction: Legionella pneumophila is one of the main causative agents of community- and hospital-acquired pneumonia. Inhalation of sprays potentially contaminated with the bacterium, due to the colonization of networks and other systems using water, is a hazard to the health of exposed individuals. Objective: Evaluate the viability of L. pneumophila in samples of water stored at various time intervals for the microbiological culture diagnosis of Legionella spp. Methods: Water samples were artificially contaminated with two strains of L. pneumophila from different serogroups and a mixture of them, for a total of 15 samples. The contaminated vessels were processed at 24 h, 72 h, 7 d, 14 d and 21 d. Microbiological culture was performed in compliance with ISO 11731: 2004 and PNO 03-013: 2015. Results: The bacterium was found to be viable in samples stored up to 21 days. The filtration concentration method obtained the greatest amount of the microorganism. Conclusions: Storage time of the samples affects the viability of L. pneumophila. The study lays the foundations for further research about the validity of L. pneumophila diagnosis as part of the service offered by the Civil Defense Scientific Research Center in Legionella spp. prevention and control programs for tourist and industrial facilities(AU)

Gasdermin-D and Caspase-7 are the key Caspase-1/8 substrates downstream of the NAIP5/NLRC4 inflammasome required for restriction of Legionella pneumophila.

Inflammasomes are cytosolic multi-protein complexes that detect infection or cellular damage and activate the Caspase-1 (CASP1) protease. The NAIP5/NLRC4 inflammasome detects bacterial flagellin and is essential for resistance to the flagellated intracellular bacterium Legionella pneumophila. The effectors required downstream of NAIP5/NLRC4 to restrict bacterial replication remain unclear. Upon NAIP5/NLRC4 activation, CASP1 cleaves and activates the pore-forming protein Gasdermin-D (GSDMD) and the effector caspase-7 (CASP7). However, Casp1-/- (and Casp1/11-/-) mice are only partially susceptible to L. pneumophila and do not phenocopy Nlrc4-/-mice, because NAIP5/NLRC4 also activates CASP8 for restriction of L. pneumophila infection. Here we show that CASP8 promotes the activation of CASP7 and that Casp7/1/11-/- and Casp8/1/11-/- mice recapitulate the full susceptibility of Nlrc4-/- mice. Gsdmd-/- mice exhibit only mild susceptibility to L. pneumophila, but Gsdmd-/-Casp7-/- mice are as susceptible as the Nlrc4-/- mice. These results demonstrate that GSDMD and CASP7 are the key substrates downstream of NAIP5/NLRC4/CASP1/8 required for resistance to L. pneumophila.

[Occupational legionella in adults over 18 years pf age: a systematic review]. / Legionelosis ocupacional en mayores de 18 años: revisión sistemática.

The scope of this paper is to review the available scientific literature about the effects on health of occupational exposure to Legionella spp. A systematic review of the scientific literature retrieved from the MEDLINE (via PubMed), ISI-Web of Science (Institute for Scientific Information), Cochrane Library, LILCAS and SCOPUS databases through February 2015 was conducted. The key words used were ««Legionnaires' Disease¼ «Legionellosis¼ «Occupational Exposure¼ «Occupational Diseases¼. Two hundred and twenty-two references were retrieved of which, after applying inclusion/exclusion criteria, 13 complete articles were selected. Of these, 9 describe pneumonia, 4 list Pontiac Fever, 1 reveals legionellosis and 3 result in death. The main causative agent of disease in workers exposed was Legionella pneumophila serogroup 1. Legionella spp infection is closely related to professions where there is nebulization with water, mainly among workers subjected to long exposure or even re-exposure. Outbreaks occurs seasonally, especially in the hottest months.

El objetivo es revisar la literatura científica sobre los problemas de salud derivados de la exposición laboral a Legionella spp. Revisión sistemática de la literatura científica recogida en las bases de datos MEDLINE (Pubmed), ISI-Web of Science (Institute for Scientific Information), Cochrane Library Plus, Literatura Latinoamericana de Información en Ciencias de la Salud (LILACS) y SCOPUS, hasta febrero 2015. Los descriptores utilizados fueron: "Legionnaires' Disease" "Legionellosis" "Occupational Exposure" "Occupational Diseases". Se obtuvieron 222 referencias, que tras aplicar los criterios de inclusión y exclusión, se seleccionaron 13 artículos a texto completo. De ellos 9 artículos describen la aparición de neumonía, 4 Fiebre de Pontiac, 1 legionelosis o presunta legionelosis y 3 muerte. El principal agente causal en los profesionales expuestos fue Legionella pneumophila serogrupo 1. La infección por legionela está ligada a las profesiones donde existe nebulización por agua, principalmente en los trabajadores sometidos a largas exposiciones o incluso a la re-exposición. Los brotes se producen de forma estacional, sobre todo en los meses más cálidos.

Legionelosis ocupacional en mayores de 18 años: revisión sistemática / Occupational legionella in adults over 18 years pf age: a systematic review

Resumen El objetivo es revisar la literatura científica sobre los problemas de salud derivados de la exposición laboral a Legionella spp. Revisión sistemática de la literatura científica recogida en las bases de datos MEDLINE (Pubmed), ISI-Web of Science (Institute for Scientific Information), Cochrane Library Plus, Literatura Latinoamericana de Información en Ciencias de la Salud (LILACS) y SCOPUS, hasta febrero 2015. Los descriptores utilizados fueron: "Legionnaires' Disease" "Legionellosis" "Occupational Exposure" "Occupational Diseases". Se obtuvieron 222 referencias, que tras aplicar los criterios de inclusión y exclusión, se seleccionaron 13 artículos a texto completo. De ellos 9 artículos describen la aparición de neumonía, 4 Fiebre de Pontiac, 1 legionelosis o presunta legionelosis y 3 muerte. El principal agente causal en los profesionales expuestos fue Legionella pneumophila serogrupo 1. La infección por legionela está ligada a las profesiones donde existe nebulización por agua, principalmente en los trabajadores sometidos a largas exposiciones o incluso a la re-exposición. Los brotes se producen de forma estacional, sobre todo en los meses más cálidos.

Abstract The scope of this paper is to review the available scientific literature about the effects on health of occupational exposure to Legionella spp. A systematic review of the scientific literature retrieved from the MEDLINE (via PubMed), ISI-Web of Science (Institute for Scientific Information), Cochrane Library, LILCAS and SCOPUS databases through February 2015 was conducted. The key words used were ««Legionnaires' Disease¼ «Legionellosis¼ «Occupational Exposure¼ «Occupational Diseases¼. Two hundred and twenty-two references were retrieved of which, after applying inclusion/exclusion criteria, 13 complete articles were selected. Of these, 9 describe pneumonia, 4 list Pontiac Fever, 1 reveals legionellosis and 3 result in death. The main causative agent of disease in workers exposed was Legionella pneumophila serogroup 1. Legionella spp infection is closely related to professions where there is nebulization with water, mainly among workers subjected to long exposure or even re-exposure. Outbreaks occurs seasonally, especially in the hottest months.

Urinary antigen testing in community-acquired pneumonia in adults: an update.

INTRODUCTION: Community-acquired pneumonia (CAP) continues to be a leading cause of hospitalization and mortality worldwide. Streptococcus pneumoniae and Legionella pneumophila remain the major etiological agents and are responsible for a significant proportion of CAP mortality. Among diagnostic tests for CAP, urine antigen detection of S. pneumoniae and L. pneumophila is widely accepted due to the simplicity of collection and the rapidity of the test results. Areas covered: This comprehensive review outlines the urinary antigen tests available, discusses their sensitivity and specificity, and assesses the usefulness of their results as the basis for targeted therapy. Expert commentary: There have been advances in urine antigen detection tests for patients with CAP. New methodologies show greater sensitivity, detect S. pneumoniae and L. pneumophila in a single test, and also detect pneumococcal serotypes. In addition, urine antigen detection tests have shown a high specificity, which means that a positive result practically indicates the causative pathogen of CAP. Therefore, a positive result can lead to a targeted therapy that is likely to improve patient outcomes and reduce the risk of resistance and adverse events. However, well-designed studies are needed to evaluate the usefulness of urine antigen detection tests with regard to clinical outcomes.

An investigation of virulence factors of Legionella pneumophila environmental isolates

ABSTRACT Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila.

An investigation of virulence factors of Legionella pneumophila environmental isolates.

Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila.

Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome.

Legionella pneumophila is a Gram-negative, flagellated bacterium that survives in phagocytes and causes Legionnaires' disease. Upon infection of mammalian macrophages, cytosolic flagellin triggers the activation of Naip/NLRC4 inflammasome, which culminates in pyroptosis and restriction of bacterial replication. Although NLRC4 and caspase-1 participate in the same inflammasome, Nlrc4-/- mice and their macrophages are more permissive to L. pneumophila replication compared with Casp1/11-/-. This feature supports the existence of a pathway that is NLRC4-dependent and caspase-1/11-independent. Here, we demonstrate that caspase-8 is recruited to the Naip5/NLRC4/ASC inflammasome in response to flagellin-positive bacteria. Accordingly, caspase-8 is activated in Casp1/11-/- macrophages in a process dependent on flagellin, Naip5, NLRC4 and ASC. Silencing caspase-8 in Casp1/11-/- cells culminated in macrophages that were as susceptible as Nlrc4-/- for the restriction of L. pneumophila replication. Accordingly, macrophages and mice deficient in Asc/Casp1/11-/- were more susceptible than Casp1/11-/- and as susceptible as Nlrc4-/- for the restriction of infection. Mechanistically, we found that caspase-8 activation triggers gasdermin-D-independent pore formation and cell death. Interestingly, caspase-8 is recruited to the Naip5/NLRC4/ASC inflammasome in wild-type macrophages, but it is only activated when caspase-1 or gasdermin-D is inhibited. Our data suggest that caspase-8 activation in the Naip5/NLRC4/ASC inflammasome enable induction of cell death when caspase-1 or gasdermin-D is suppressed.

Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone.

Patients with infantile spasms, an intractable epileptic disorder, often are treated with adrenocorticotropic hormone. Legionella pneumophila is a rare cause of pneumonia in children. We describe 2 infants with Legionella pneumonia whose infection occurred within 1 month after starting adrenocorticotropic hormone.

[Prognostic factors in adult patients hospitalized for pneumonia caused by Legionella pneumophila]. / Factores pronósticos en adultos hospitalizados por neumonía causada por Legionella pneumophila.

INTRODUCTION: Legionellosis is a multisystem bacterial disease, which causes pneumonia with high mortality in patients with comorbidity and admitted in intensive care units (ICU). OBJECTIVE: Determine predictors of mortality or ICU admission. METHODS: Retrospective follow-up of patients diagnosed with Legionella pneumophila pneumonia in Complexo Hospitalario Universitario de A Coruña. Period 2000-2013 (n=240). Analysis of multivariate logistic regression was performed. RESULTS: Mean age was 57.2±15.4 years old, 88.3% were male. Average score of comorbidity (Charlson score) was 2.3±2.3. There was a clear seasonal variation. Predominant symptoms were fever (92.5%), dry cough (38.1%) and dyspnea (33.9%). Creatinine clearance was lower than 60 mL/min/1.73 m² in 29.7% and sodium<135 mEq/l in 58.3%. Admission to ICU rate was 16.3% and 10.8% needs mechanical ventilation. Inhospital mortality rate was 4.6%, rising to 23.1% in patients admitted to ICU. Variables associated to predict ICU admission were age (OR=0.96), liver disease (OR=7.13), dyspnea (OR=4.33), delirium (OR=5.86) and high levels of lactatedehydrogenase (OR=1.002). Variables associated with inhospital mortality were Charlson index (OR=1.70), mechanical ventilation (OR=31.44) and high levels of lactatedehydrogenase (OR=1.002). DISCUSSION: Younger patients with liver disease, dyspnea and confusion are more likely to be admitted to ICU. Comorbidity, mechanical ventilation and elevated LDH levels are associated with higher mortality rate.

Caspase-1 but Not Caspase-11 Is Required for NLRC4-Mediated Pyroptosis and Restriction of Infection by Flagellated Legionella Species in Mouse Macrophages and In Vivo.

Gram-negative bacteria from the Legionella genus are intracellular pathogens that cause a severe form of pneumonia called Legionnaires' disease. The bacteria replicate intracellularly in macrophages, and the restriction of bacterial replication by these cells is critical for host resistance. The activation of the NAIP5/NLRC4 inflammasome, which is readily triggered in response to bacterial flagellin, is essential for the restriction of bacterial replication in murine macrophages. Once activated, this inflammasome induces pore formation and pyroptosis and facilitates the restriction of bacterial replication in macrophages. Because investigations related to the NLRC4-mediated restriction of Legionella replication were performed using mice double deficient for caspase-1 and caspase-11, we assessed the participation of caspase-1 and caspase-11 in the functions of the NLRC4 inflammasome and the restriction of Legionella replication in macrophages and in vivo. By using several species of Legionella and mice singly deficient for caspase-1 or caspase-11, we demonstrated that caspase-1 but not caspase-11 was required for pore formation, pyroptosis, and restriction of Legionella replication in macrophages and in vivo. By generating F1 mice in a mixed 129 × C57BL/6 background deficient (129 × Casp-11(-/-) ) or sufficient (129 × C57BL/6) for caspase-11 expression, we found that caspase-11 was dispensable for the restriction of Legionella pneumophila replication in macrophages and in vivo. Thus, although caspase-11 participates in flagellin-independent noncanonical activation of the NLRP3 inflammasome, it is dispensable for the activities of the NLRC4 inflammasome. In contrast, functional caspase-1 is necessary and sufficient to trigger flagellin/NLRC4-mediated restriction of Legionella spp. infection in macrophages and in vivo.