RESUMEN
Allergic immunity is orchestrated by group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells prominently arrayed at epithelial- and microbial-rich barriers. However, ILC2s and Th2 cells are also present in fibroblast-rich niches within the adventitial layer of larger vessels and similar boundary structures in sterile deep tissues, and it remains unclear whether they undergo dynamic repositioning during immune perturbations. Here, we used thick-section quantitative imaging to show that allergic inflammation drives invasion of lung and liver non-adventitial parenchyma by ILC2s and Th2 cells. However, during concurrent type 1 and type 2 mixed inflammation, IFNγ from broadly distributed type 1 lymphocytes directly blocked both ILC2 parenchymal trafficking and subsequent cell survival. ILC2 and Th2 cell confinement to adventitia limited mortality by the type 1 pathogen Listeria monocytogenes. Our results suggest that the topography of tissue lymphocyte subsets is tightly regulated to promote appropriately timed and balanced immunity.
Asunto(s)
Inflamación/inmunología , Interferón gamma/inmunología , Subgrupos Linfocitarios/inmunología , Células Th2/inmunología , Animales , Muerte Celular/inmunología , Movimiento Celular/inmunología , Hipersensibilidad/inmunología , Inmunidad Innata , Interleucina-33/inmunología , Interleucina-5/metabolismo , Listeria monocytogenes , Listeriosis/inmunología , Listeriosis/mortalidad , Hígado/inmunología , Pulmón/inmunología , Subgrupos Linfocitarios/metabolismo , Lisofosfolípidos/inmunología , Ratones , Tejido Parenquimatoso/inmunología , Esfingosina/análogos & derivados , Esfingosina/inmunología , Células TH1/inmunología , Células Th2/metabolismoRESUMEN
Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states. VIDEO ABSTRACT.
Asunto(s)
Manejo de la Enfermedad , Ayuno , Glucosa/metabolismo , Conducta de Enfermedad/fisiología , Gripe Humana/metabolismo , Listeriosis/metabolismo , Apoyo Nutricional/efectos adversos , Animales , Antimetabolitos/uso terapéutico , Células Cultivadas , Desoxiglucosa/uso terapéutico , Glucosa/administración & dosificación , Humanos , Inflamación , Gripe Humana/fisiopatología , Gripe Humana/terapia , Lipopolisacáridos , Listeriosis/mortalidad , Listeriosis/fisiopatología , Listeriosis/terapia , Masculino , Ratones , Ratones Endogámicos C57BL , Poli I-C , Sepsis/inducido químicamente , Sepsis/prevención & control , Factor de Transcripción CHOP/metabolismoRESUMEN
Neutrophils express Toll-like receptors (TLRs) for the recognition of conserved bacterial elements to initiate antimicrobial responses. However, whether other cytosolic DNA sensors are expressed by neutrophils remains elusive. Here we found constitutive expression of the transcription factor Sox2 in the cytoplasm of mouse and human neutrophils. Neutrophil-specific Sox2 deficiency exacerbated bacterial infection. Sox2 directly recognized microbial DNA through its high-mobility-group (HMG) domain. Upon challenge with bacterial DNA, Sox2 dimerization was needed to activate a complex of the kinase TAK1 and its binding partner TAB2, which led to activation of the transcription factors NF-κB and AP-1 in neutrophils. Deficiency in TAK1 or TAB2 impaired Sox2-mediated antibacterial immunity. Overall, we reveal a previously unrecognized role for Sox2 as a cytosolic sequence-specific DNA sensor in neutrophils, which might provide potential therapeutic strategies for the treatment of infectious diseases.
Asunto(s)
ADN Bacteriano/inmunología , Inmunidad Innata , Listeriosis/inmunología , Neutrófilos/inmunología , Factores de Transcripción SOXB1/inmunología , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Animales , Citoplasma/inmunología , Citoplasma/microbiología , Regulación de la Expresión Génica , Humanos , Listeria monocytogenes/inmunología , Listeriosis/genética , Listeriosis/microbiología , Listeriosis/mortalidad , Quinasas Quinasa Quinasa PAM/deficiencia , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/inmunología , Ratones , FN-kappa B/genética , FN-kappa B/inmunología , Neutrófilos/microbiología , Multimerización de Proteína , Factores de Transcripción SOXB1/genética , Transducción de Señal , Análisis de Supervivencia , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/inmunologíaRESUMEN
PURPOSE: Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. METHODS: We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. RESULTS: In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81% vs. 20%). The 90-day mortality was with significantly lower in the gentamicin combination treatment group (10%) compared to the monotherapy group (60%). Multivariable cox regression analysis, adjusted for a propensity score computed based on neurolisteriosis, aaCCI and sex, revealed a significantly reduced hazard ratio of 0.07 (95% CI: 0.01-0.53, p = 0.01) for 90-day mortality for the gentamicin combination treatment. CONCLUSION: This retrospective study highlights the benefit of gentamicin combination treatment in reducing the 90-day mortality rate among patients with invasive listeriosis. The high prevalence of monotherapy in this study cohort raises concerns about the adequacy of antibiotic therapy in clinical practice.
Asunto(s)
Antibacterianos , Quimioterapia Combinada , Gentamicinas , Listeriosis , Humanos , Gentamicinas/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Anciano , Antibacterianos/uso terapéutico , Listeriosis/tratamiento farmacológico , Listeriosis/mortalidad , Persona de Mediana Edad , Anciano de 80 o más Años , Listeria monocytogenes/efectos de los fármacosRESUMEN
BACKGROUND: An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS: We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS: A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections. CONCLUSIONS: This investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.
Asunto(s)
Brotes de Enfermedades , Enfermedades Transmitidas por los Alimentos/epidemiología , Listeria monocytogenes/aislamiento & purificación , Listeriosis/epidemiología , Productos de la Carne/microbiología , Adolescente , Adulto , Anciano , Técnicas de Tipificación Bacteriana , Estudios de Casos y Controles , Femenino , Enfermedades Transmitidas por los Alimentos/etiología , Enfermedades Transmitidas por los Alimentos/mortalidad , Infecciones por VIH/complicaciones , VIH-1 , Humanos , Recién Nacido , Listeria monocytogenes/genética , Listeriosis/etiología , Listeriosis/mortalidad , Masculino , Productos de la Carne/efectos adversos , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Recall y Retirada del Producto , Distribución por Sexo , Sudáfrica/epidemiología , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
The mucin Muc2 is a major constituent of the mucus layer that covers the intestinal epithelium and creates a barrier between epithelial cells and luminal commensal or pathogenic microorganisms. The Gram-positive foodborne pathogen Listeria monocytogenes can cause enteritis and also disseminate from the intestine to give rise to systemic disease. L. monocytogenes can bind to intestinal Muc2, but the influence of the Muc2 mucin barrier on L. monocytogenes intestinal colonization and systemic dissemination has not been explored. Here, we used an orogastric L. monocytogenes infection model to investigate the role of Muc2 in host defense against L. monocytogenes Compared to wild-type mice, we found that Muc2-/- mice exhibited heightened susceptibility to orogastric challenge with L. monocytogenes, with higher mortality, elevated colonic pathology, and increased pathogen burdens in both the intestinal tract and distal organs. In contrast, L. monocytogenes burdens were equivalent in wild-type and Muc2-/- animals when the pathogen was administered intraperitoneally, suggesting that systemic immune defects related to Muc2 deficiency do not explain the heightened pathogen dissemination observed in oral infections. Using a barcoded L. monocytogenes library to measure intrahost pathogen population dynamics, we found that Muc2-/- animals had larger pathogen founding population sizes in the intestine and distal sites than observed in wild-type animals. Comparisons of barcode frequencies suggested that the colon becomes the major source for seeding the internal organs in Muc2-/- animals. Together, our findings reveal that Muc2 mucin plays a key role in controlling L. monocytogenes colonization, dissemination, and population dynamics.
Asunto(s)
Listeria monocytogenes , Listeriosis/microbiología , Mucina 2/deficiencia , Animales , Carga Bacteriana , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Genotipo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Listeria monocytogenes/inmunología , Listeriosis/genética , Listeriosis/mortalidad , Ratones , Ratones Noqueados , Mortalidad , Especificidad de ÓrganosRESUMEN
IFNγ is a cytokine that plays a key role in host defense against intracellular pathogens. In addition to the canonical JAK-STAT1 pathway, IFNγ also activates an IKKß-mediated noncanonical signaling pathway that is essential for induction of a subset of downstream effector genes. The molecular mechanisms and functional significance of this IFNγ-triggered noncanonical pathway remains enigmatic. Here, we identified sorting nexin 8 (SNX8) as an important component of the IFNγ-triggered noncanonical signaling pathway. SNX8-deficiency impaired IFNγ-triggered induction of a subset of downstream genes. Snx8-/- mice infected with Listeria monocytogenes exhibited lower serum cytokine levels and higher bacterial loads in the livers and spleens, resulting in higher lethality. Mechanistically, SNX8 interacted with JAK1 and IKKß and promoted their association. IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKß to the JAK1 complex. SNX8-deficiency impaired IFNγ-induced oligomerization and autophosphorylation of IKKß at Ser177, which is critical for selective induction of downstream genes. Our findings suggest that SNX8 acts as a link for IFNγ-triggered noncanonical signaling pathway, which induces a subset of downstream genes important for host defense against L. monocytogenes infection.
Asunto(s)
Quinasa I-kappa B/inmunología , Janus Quinasa 1/inmunología , Listeria monocytogenes/patogenicidad , Listeriosis/genética , Nexinas de Clasificación/inmunología , Animales , Carga Bacteriana , Regulación de la Expresión Génica , Células HEK293 , Células HeLa , Humanos , Quinasa I-kappa B/deficiencia , Quinasa I-kappa B/genética , Interferón gamma/genética , Interferón gamma/inmunología , Janus Quinasa 1/genética , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Listeriosis/microbiología , Listeriosis/mortalidad , Hígado/inmunología , Hígado/microbiología , Ratones , Ratones Noqueados , Peptidoglicano/administración & dosificación , Fosforilación , Transducción de Señal , Nexinas de Clasificación/deficiencia , Nexinas de Clasificación/genética , Bazo/inmunología , Bazo/microbiología , Análisis de Supervivencia , Células THP-1RESUMEN
Little evidence exists addressing the clinical value of adding gentamicin to ampicillin for invasive listeriosis. A multicenter retrospective observational study of nonpregnant adult patients with invasive listeriosis (primary bacteremia, central nervous system (CNS) disease, and others) in 11 hospitals in Israel between the years 2008 and 2014 was conducted. We evaluated the effect of penicillin-based monotherapy compared with early combination therapy with gentamicin, defined as treatment started within 48 h of culture results and continued for a minimum of 7 days. Patients who died within 48 h of the index culture were excluded. The primary outcome was 30-day all-cause mortality. A total of 190 patients with invasive listeriosis were included. Fifty-nine (30.6%) patients were treated with early combination therapy, 90 (46.6%) received monotherapy, and 44 (22.8%) received other treatments. Overall 30-day mortality was 20.5% (39/190). Factors associated with mortality included lower baseline functional status, congestive heart failure, and higher sequential organ failure assessment score. Source of infection, treatment type, and time from culture taken date to initiation of effective therapy were not associated with mortality. In multivariable analysis, monotherapy was not significantly associated with increased 30-day mortality compared with early combination therapy (OR 1.947, 95% CI 0.691-5.487). Results were similar in patients with CNS disease (OR 3.037, 95% CI 0.574-16.057) and primary bacteremia (OR 2.983, 95% CI 0.575-15.492). In our retrospective cohort, there was no statistically significant association between early combination therapy and 30-day mortality. A randomized controlled trial may be necessary to assess optimal treatment.
Asunto(s)
Ampicilina/uso terapéutico , Antibacterianos/uso terapéutico , Gentamicinas/uso terapéutico , Listeriosis/tratamiento farmacológico , Listeriosis/mortalidad , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Israel/epidemiología , Listeria/efectos de los fármacos , Listeria/aislamiento & purificación , Listeriosis/diagnóstico , Listeriosis/patología , Masculino , Persona de Mediana Edad , Mortalidad , Oportunidad Relativa , Estudios RetrospectivosRESUMEN
Background: Neurolisteriosis ranks among the most severe neurological infections. Its radiological features have not been thoroughly studied. We describe here the neuroradiological features of neurolisteriosis and assess their prognostic value. Methods: Patients with microbiologically proven neurolisteriosis were enrolled from November 2009 to October 2013 in MONALISA study. Magnetic resonance and computed tomography images were studied by 2 independent neuroradiologists. Predictors of 3-month mortality were determined using logistic regression. Results: Seventy-one patients were included; 42 were men (59%). Mean age was 64 years. Sixty patients (85%) reported signs of encephalitis, with clinical brainstem involvement in 16 (23%). Images were abnormal in 87% of cases (62/71). Main neuroradiological images were meningeal enhancement (25/71, 35%), abscess(es), or nodular image(s) evocative of abscess (10/71, 14%), hemorrhages (11/71, 15%), contrast-enhancing ventricles, or hydrocephalus (7/71, 10%). White-matter images (42/71, 59%), dilated Virchow-Robin spaces (22/71, 31%), and cerebral atrophy were also reported (34/71, 48%). Brainstem involvement (meningeal enhancement, abscess) was reported in only 7/71 cases (10%). Three-month survival was lower in patients with hydrocephalus or contrast-enhancing ventricles (1/7 [14%] than without [47/64, 73%], P = .005) and in patients with parenchymal images (abscess[es], nodule[s]\, or white matter images; 25/46 [54%] vs 23/25 without [92%], P = .004). Parenchymal images were associated with lower 3-month survival in the multivariable model (odds ratio 5.60, 95% confidence interval [1.42-29.6], P = .02). Conclusions: Neurolisteriosis presents as a combination of neuroradiological images, none being specific. Radiological signs of rhombencephalitis are uncommon, whereas, unexpectedly, hemorrhagic images are frequent. The negative prognostic value of parenchymal neuroradiological images was evidenced. Clinical Trials Registration: NCT01520597.
Asunto(s)
Encefalopatías/diagnóstico por imagen , Encefalitis/diagnóstico por imagen , Listeriosis/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Encefalopatías/microbiología , Encefalitis/microbiología , Femenino , Humanos , Listeria monocytogenes/aislamiento & purificación , Listeriosis/mortalidad , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Listeria (L.) monocytogenes as the causative agent of listeriosis in humans and different animal species, has its reservoir in the environment. It can be found in the gut and faeces of healthy pigs, but under certain circumstances it may cause clinical disease. Fatteners are usually not known to get affected by Listeria-associated septicaemia and enteritis. This case report shows, that L. monocytogenes should be part of the list of differential diagnoses, when fattening pigs suffer from haemorrhagic diarrhoea and septicaemia. CASE PRESENTATION: Here, we report of an episode of fatal listeriosis in fattening pigs in a piglet producing farm in Lower Austria, which was combined with a fattening unit with space for 450 fatteners. The mortality rate resulted in 7.8% among fattening pigs after suffering from clinical symptoms such as anorexia, bloody diarrhoea and increased body temperature. Two fattening pigs with clinical symptoms and maize silage samples were used for further diagnostics. L. monocytogenes were isolated from serosa samples of the pigs and in the corresponding fed maize silage. One animal was positively tested for Brachyspira hyodysenteriae, which may have also been involved in the development of colitis. Immunohistochemically, L. monocytogenes could be detected in high amounts in lymphatic tissue of the gut. Molecular biological characterisation of the L. monocytogenes isolates from pigs and maize silage resulted in an identical DNA-fingerprint assigned to sequence type (ST) 21. Additionally, a high content of deoxynivalenol (3000 parts per billion) was found in maize silage. Therefore, the maize silage produced under inappropriate ensilaging conditions in a silo, was most likely the source of infection. Antimicrobial therapy with amoxicillin led to a fast cure of the remaining affected fatteners. CONCLUSION: To conclude, we were able to show, that L. monocytogenes can cause clinical disease in finishing pigs, which may have been a result of immunosuppression due to high deoxynivalenol exposure. When feeding silage it is important that all ensilaging procedures occur under appropriate anaerobic conditions to guarantee suppression of listerial growth.
Asunto(s)
Alimentación Animal/efectos adversos , Listeriosis/veterinaria , Enfermedades de los Porcinos/etiología , Alimentación Animal/microbiología , Animales , Listeria monocytogenes , Listeriosis/mortalidad , Ensilaje , Porcinos , Enfermedades de los Porcinos/mortalidadRESUMEN
The ability of pathogens to influence host cell survival is a crucial virulence factor. Listeria monocytogenes (Lm) infection is known to be associated with severe apoptosis of hepatocytes and spleen cells. This impairs host defense mechanisms and thereby facilitates the spread of intracellular pathogens. The general mechanisms of apoptosis elicited by Lm infection are understood, however, the roles of BH3-only proteins during primary Lm infection have not been examined. To explore the roles of BH3-only proteins in Lm-induced apoptosis, we studied Listeria infections in mice deficient in Bim, Bid, Noxa or double deficient in BimBid or BimNoxa. We found that BimNoxa double knockout mice were highly resistant to high-dose challenge with Listeria. Decreased bacterial burden and decreased host cell apoptosis were found in the spleens of these mice. The ability of the BH3-deficient mice to clear bacterial infection more efficiently than WT was correlated with increased concentrations of ROS, neutrophil extracellular DNA trap release and downregulation of TNF-α. Our data show a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic host cell death during Listeria infection.
Asunto(s)
Apoptosis , Listeria monocytogenes , Listeriosis/etiología , Listeriosis/metabolismo , Proteínas Mitocondriales/metabolismo , Animales , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/deficiencia , Proteína 11 Similar a Bcl2/deficiencia , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Susceptibilidad a Enfermedades , Trampas Extracelulares/inmunología , Femenino , Expresión Génica , Listeriosis/mortalidad , Listeriosis/patología , Masculino , Ratones , Ratones Noqueados , Infiltración Neutrófila/genética , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/deficiencia , Especies Reactivas de Oxígeno/metabolismo , Bazo/inmunología , Bazo/metabolismo , Bazo/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Cellular glucose uptake may involve either non-concentrative glucose carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which accumulates glucose against glucose gradients and may thus accomplish cellular glucose uptake even at dramatically decreased extracellular glucose concentrations. SGLT1 is not only expressed in epithelia but as well in tumour cells and immune cells. Immune cell functions strongly depend on their metabolism, therefore we hypothesized that deficiency of SGLT1 modulates the defence against bacterial infection. To test this hypothesis, we infected wild type mice and gene targeted mice lacking functional SGLT1 with Listeria monocytogenes. METHODS: SGLT1 deficient mice and wild type littermates were infected with 1x104 CFU Listeria monocytogenes intravenously. Bacterial titers were determined by colony forming assay, SGLT1, TNF-α, IL-6 and IL-12a transcript levels were determined by qRT-PCR, as well as SGLT1 protein abundance and localization by immunohistochemistry. RESULTS: Genetic knockout of SGLT1 (Slc5a1-/- mice) significantly compromised bacterial clearance following Listeria monocytogenes infection with significantly enhanced bacterial load in liver, spleen, kidney and lung, and significantly augmented hepatic expression of TNF-α and IL-12a. While all wild type mice survived, all SGLT1 deficient mice died from the infection. CONCLUSIONS: SGLT1 is required for bacterial clearance and host survival following murine Listeria infection.
Asunto(s)
Expresión Génica/inmunología , Glucosa/inmunología , Listeriosis/genética , Listeriosis/mortalidad , Hígado/inmunología , Transportador 1 de Sodio-Glucosa/inmunología , Animales , Carga Bacteriana , Transporte Biológico , Glucosa/metabolismo , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Riñón/inmunología , Riñón/microbiología , Riñón/patología , Listeria monocytogenes , Listeriosis/inmunología , Listeriosis/microbiología , Hígado/microbiología , Hígado/patología , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/genética , ARN Mensajero/inmunología , Transportador 1 de Sodio-Glucosa/deficiencia , Transportador 1 de Sodio-Glucosa/genética , Bazo/inmunología , Bazo/microbiología , Bazo/patología , Análisis de Supervivencia , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
TNF-α-induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of cancer and infection. However, its precise roles and mechanisms of actions are not well understood. We report in this article that TNFAIP8 regulates Listeria monocytogenes infection by controlling pathogen invasion and host cell apoptosis in a RAC1 GTPase-dependent manner. TNFAIP8-knockout mice were resistant to lethal L. monocytogenes infection and had reduced bacterial load in the liver and spleen. TNFAIP8 knockdown in murine liver HEPA1-6 cells increased apoptosis, reduced bacterial invasion into cells, and resulted in dysregulated RAC1 activation. TNFAIP8 could translocate to plasma membrane and preferentially associate with activated RAC1-GTP. The combined effect of reduced bacterial invasion and increased sensitivity to TNF-α-induced clearance likely protected the TNFAIP8-knockout mice from lethal listeriosis. Thus, by controlling bacterial invasion and the death of infected cells through RAC1, TNFAIP8 regulates the pathogenesis of L. monocytogenes infection.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Apoptosis/genética , Listeria monocytogenes/inmunología , Listeriosis/genética , Listeriosis/inmunología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Guanosina Trifosfato/metabolismo , Listeriosis/metabolismo , Listeriosis/mortalidad , Ratones , Ratones Noqueados , Modelos Biológicos , Unión Proteica , Factor de Necrosis Tumoral alfa/metabolismo , Proteína de Unión al GTP rac1/metabolismoRESUMEN
Listeria monocytogenes is a foodborne pathogen that contaminates food-processing environments and persists within biofilms on equipment, utensils, floors, and drains, ultimately reaching final products by cross-contamination. This pathogen grows even under high salt conditions or refrigeration temperatures, remaining viable in various food products until the end of their shelf life. While the estimated incidence of listeriosis is lower than other enteric illnesses, infections caused by L. monocytogenes are more likely to lead to hospitalizations and fatalities. Despite the description of L. monocytogenes occurrence in Brazilian food-processing facilities and foods, there is a lack of consistent data regarding listeriosis cases and outbreaks directly associated with food consumption. Listeriosis requires rapid treatment with antibiotics and most drugs suitable for Gram-positive bacteria are effective against L. monocytogenes. Only a minority of clinical antibiotic-resistant L. monocytogenes strains have been described so far; whereas many strains recovered from food-processing facilities and foods exhibited resistance to antimicrobials not suitable against listeriosis. L. monocytogenes control in food industries is a challenge, demanding proper cleaning and application of sanitization procedures to eliminate this foodborne pathogen from the food-processing environment and ensure food safety. This review focuses on presenting the L. monocytogenes distribution in food-processing environment, food contamination, and control in the food industry, as well as the consequences of listeriosis to human health, providing a comparison of the current Brazilian situation with the international scenario.
Asunto(s)
Microbiología de Alimentos , Listeria monocytogenes/aislamiento & purificación , Listeriosis/epidemiología , Brasil/epidemiología , Brotes de Enfermedades , Contaminación de Alimentos , Industria de Procesamiento de Alimentos , Humanos , Listeriosis/mortalidad , Listeriosis/prevención & controlRESUMEN
Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0-825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March-October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.
Asunto(s)
Queso/microbiología , Brotes de Enfermedades , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/epidemiología , Listeria monocytogenes/aislamiento & purificación , Listeriosis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Enfermedades Transmitidas por los Alimentos/microbiología , Enfermedades Transmitidas por los Alimentos/mortalidad , Humanos , Listeria monocytogenes/clasificación , Listeriosis/microbiología , Listeriosis/mortalidad , Masculino , Persona de Mediana Edad , Embarazo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Listeriosis is a rare disease caused by the bacterium Listeria monocytogenes and mainly affects at risk people. Listeriosis can lead to sepsis, central nervous system (CNS) infections and death. The objectives of this study were to describe and quantify comorbidities and neurological sequelae underlying non-perinatal listeriosis cases and to describe the factors associated with death and CNS infections in non-perinatal listeriosis. METHODS: We retrospectively collected clinical data through computerized, paper or microfilmed medical records in two Belgian university hospitals. Logistic regression models and likelihood ratio tests allowed identifying factors associated with death and CNS infections. RESULTS: Sixty-four cases of non-perinatal listeriosis were included in the clinical case series and 84 % were affected by at least one comorbid condition. The main comorbidities were cancer, renal and severe cardio-vascular diseases. Twenty-nine patients (45 %) suffered from a CNS infection and 14 patients (22 %) died during hospitalization, among whom six (43 %) had a CNS involvement. Among surviving patients, eleven suffered from neurological sequelae (22 %) at hospital discharge; all had CNS infection. Five of these patients (45 %) still suffered of their neurological sequelae after a median follow-up of one year (range: 0.08-19). The factor associated with death during the hospitalization was the presence of a severe cardiovascular disease (OR = 4.72, p = 0.015). Two factors inversely related with CNS infections were antibiotic monotherapy (OR = 0.28, p = 0.04) and the presence of renal disease (OR = 0.18, p = 0.02). CONCLUSIONS: In a public health context these results could be a starting point for future burden of listeriosis studies taking into account comorbidity.
Asunto(s)
Infecciones del Sistema Nervioso Central/epidemiología , Listeria monocytogenes , Listeriosis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Infecciones del Sistema Nervioso Central/complicaciones , Infecciones del Sistema Nervioso Central/mortalidad , Niño , Preescolar , Comorbilidad , Femenino , Hospitales Universitarios , Humanos , Lactante , Recién Nacido , Listeriosis/complicaciones , Listeriosis/mortalidad , Modelos Logísticos , Masculino , Registros Médicos , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
Listeria monocytogenes is a major cause of mortality resulting from food poisoning in the United States. In mice, C5 has been genetically linked to host resistance to listeriosis. Despite this genetic association, it remains poorly understood how C5 and its activation products, C5a and C5b, confer host protection to this Gram-positive intracellular bacterium. In this article, we show in a systemic infection model that the major receptor for C5a, C5aR1, is required for a normal robust host immune response against L. monocytogenes. In comparison with wild-type mice, C5aR1(-/-) mice had reduced survival and increased bacterial burden in their livers and spleens. Infected C5aR1(-/-) mice exhibited a dramatic reduction in all major subsets of splenocytes, which was associated with elevated caspase-3 activity and increased TUNEL staining. Because type 1 IFN has been reported to impede the host response to L. monocytogenes through the promotion of splenocyte death, we examined the effect of C5aR1 on type 1 IFN expression in vivo. Indeed, serum levels of IFN-α and IFN-ß were significantly elevated in L. monocytogenes-infected C5aR1(-/-) mice. Similarly, the expression of TRAIL, a type 1 IFN target gene and a proapoptotic factor, was elevated in NK cells isolated from infected C5aR1(-/-) mice. Treatment of C5aR1(-/-) mice with a type 1 IFNR blocking Ab resulted in near-complete rescue of L. monocytogenes-induced mortality. Thus, these findings reveal a critical role for C5aR1 in host defense against L. monocytogenes through the suppression of type 1 IFN expression.
Asunto(s)
Interferón-alfa/genética , Interferón beta/genética , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Bazo/inmunología , Anafilatoxinas/inmunología , Animales , Anticuerpos/farmacología , Apoptosis , Carga Bacteriana , Caspasa 3/genética , Caspasa 3/inmunología , Complemento C5a/genética , Complemento C5a/inmunología , Complemento C5b/genética , Complemento C5b/inmunología , Expresión Génica , Interferón-alfa/inmunología , Interferón beta/inmunología , Listeriosis/tratamiento farmacológico , Listeriosis/microbiología , Listeriosis/mortalidad , Hígado/inmunología , Hígado/microbiología , Hígado/patología , Linfocitos/inmunología , Linfocitos/microbiología , Linfocitos/patología , Masculino , Ratones , Ratones Noqueados , Receptor de Anafilatoxina C5a/genética , Receptor de Anafilatoxina C5a/inmunología , Receptores de Interferón/antagonistas & inhibidores , Receptores de Interferón/genética , Receptores de Interferón/inmunología , Bazo/microbiología , Bazo/patología , Análisis de Supervivencia , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/inmunologíaRESUMEN
In the first seven weeks of 2016, five serotype 1/2a Listeria monocytogenes isolates were collected from patients with invasive listeriosis in Ancona province in Italy. These strains and six 1/2a isolates identified in 2015 in the same area were typed by ERIC-PCR and PFGE. A clonal relationship, documented between the two sets of isolates, suggested a listeriosis outbreak in Ancona that started most probably in 2015. Investigation into the source of infection is still ongoing.
Asunto(s)
Brotes de Enfermedades/estadística & datos numéricos , Listeria monocytogenes/clasificación , Listeria monocytogenes/aislamiento & purificación , Listeriosis/microbiología , Listeriosis/mortalidad , Anciano , Anciano de 80 o más Años , Brotes de Enfermedades/prevención & control , Femenino , Humanos , Incidencia , Italia/epidemiología , Listeria monocytogenes/inmunología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Seroepidemiológicos , Serotipificación , Tasa de SupervivenciaRESUMEN
An outbreak of neurological disease was investigated in red-legged partridges between 8 and 28 days of age. Clinical signs included torticollis, head tilt and incoordination and over an initial eight day period approximately 30-40 fatalities occurred per day. No significant gross post mortem findings were detected. Histopathological examination of the brain and bacterial cultures followed by partial sequencing confirmed a diagnosis of encephalitis due to Listeria monocytogenes. Further isolates were obtained from follow-up carcasses, environmental samples and pooled tissue samples of newly imported day-old chicks prior to placement on farm. These isolates had the same antibiotic resistance pattern as the isolate of the initial post mortem submission and belonged to the same fluorescent amplified fragment length polymorphism (fAFLP) subtype. This suggested that the isolates were very closely related or identical and that the pathogen had entered the farm with the imported day-old chicks, resulting in disease manifestation in partridges between 8 and 28 days of age. Reports of outbreaks of encephalitic listeriosis in avian species are rare and this is to the best of our knowledge the first reported outbreak in red-legged partridges.
Asunto(s)
Enfermedades de las Aves/patología , Brotes de Enfermedades/veterinaria , Galliformes/microbiología , Encefalitis Infecciosa/veterinaria , Listeria/aislamiento & purificación , Listeriosis/veterinaria , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados/veterinaria , Animales , Antibacterianos/farmacología , Enfermedades de las Aves/microbiología , Enfermedades de las Aves/mortalidad , Encefalitis Infecciosa/microbiología , Encefalitis Infecciosa/mortalidad , Encefalitis Infecciosa/patología , Listeria/efectos de los fármacos , Listeria/genética , Listeria/inmunología , Listeriosis/microbiología , Listeriosis/mortalidad , Listeriosis/patología , Londres/epidemiología , Pruebas de Sensibilidad Microbiana , Filogenia , Análisis de Secuencia de ADN/veterinariaRESUMEN
Estimates of the economic costs associated with foodborne disease are important to inform public health decision-making. In 2008, 57 cases of listeriosis and 24 deaths in Canada were linked to contaminated delicatessen meat from one meat processing plant. Costs associated with the cases (including medical costs, nonmedical costs, and productivity losses) and those incurred by the implicated plant and federal agencies responding to the outbreak were estimated to be nearly $242 million Canadian dollars (CAD, 2008). Case costs alone were estimated at approximately $2.8 million (CAD, 2008) including loss of life. This demonstrates the considerable economic burden at both the individual and population levels associated with foodborne disease and foodborne outbreaks in particular. Foodborne outbreaks due to severe pathogens, such as Listeria monocytogenes and those that result in product recalls, are typically the most costly from the individual and/or societal perspective. Additional economic estimates of foodborne disease would contribute to our understanding of the burden of foodborne disease in Canada and would support the need for ongoing prevention and control activities.