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2.
Nat Immunol ; 22(11): 1382-1390, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34663978

RESUMO

Intergenerational inheritance of immune traits linked to epigenetic modifications has been demonstrated in plants and invertebrates. Here we provide evidence for transmission of trained immunity across generations to murine progeny that survived a sublethal systemic infection with Candida albicans or a zymosan challenge. The progeny of trained mice exhibited cellular, developmental, transcriptional and epigenetic changes associated with the bone marrow-resident myeloid effector and progenitor cell compartment. Moreover, the progeny of trained mice showed enhanced responsiveness to endotoxin challenge, alongside improved protection against systemic heterologous Escherichia coli and Listeria monocytogenes infections. Sperm DNA of parental male mice intravenously infected with the fungus C. albicans showed DNA methylation differences linked to immune gene loci. These results provide evidence for inheritance of trained immunity in mammals, enhancing protection against infections.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Infecções por Escherichia coli/imunologia , Escherichia coli/imunologia , Hereditariedade , Imunidade Inata/genética , Listeria monocytogenes/imunologia , Listeriose/imunologia , Células Mieloides/imunologia , Animais , Candida albicans/patogenicidade , Candidíase/genética , Candidíase/metabolismo , Candidíase/microbiologia , Células Cultivadas , Metilação de DNA , Modelos Animais de Doenças , Epigênese Genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Interações Hospedeiro-Patógeno , Listeria monocytogenes/patogenicidade , Listeriose/genética , Listeriose/metabolismo , Listeriose/microbiologia , Masculino , Camundongos Transgênicos , Células Mieloides/metabolismo , Células Mieloides/microbiologia , Espermatozoides/imunologia , Espermatozoides/metabolismo , Transcrição Genética
3.
Food Microbiol ; 99: 103800, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34119094

RESUMO

A quantitative microbial risk assessment (QMRA) model predicting the listeriosis risk related to the consumption of Ready- To- Eat (RTE) cooked meat products sliced at retail stores in Greece was developed. The probability of illness per serving assessed for 87 products available in the Greek market was found highly related to the nitrite concentration; products having a lower concentration showed a higher risk per serving. The predicted 95th percentiles of the annual listeriosis cases totaled 33 of which 13 cases were <65 years old and 20 cases ≥65 years old. The highest number of cases was predicted for mortadella, smoked turkey, boiled turkey and parizer, which were the most frequently consumed product categories. Two scenarios for assessing potential interventions to reduce the risk were tested: setting a use-by date of 14 days (these products have no use-by date based on current European Union legislation) and improving the temperature control during domestic storage. The two scenarios resulted in a decrease of the 95th and 99th percentiles of the total annual cases by 97% and 88%, respectively.


Assuntos
Fast Foods/microbiologia , Listeria monocytogenes/isolamento & purificação , Produtos da Carne/microbiologia , Animais , Bovinos , Galinhas , Qualidade de Produtos para o Consumidor , Feminino , Contaminação de Alimentos/análise , Contaminação de Alimentos/economia , Contaminação de Alimentos/estatística & dados numéricos , Grécia/epidemiologia , Humanos , Listeria monocytogenes/classificação , Listeria monocytogenes/genética , Listeria monocytogenes/crescimento & desenvolvimento , Listeriose/epidemiologia , Listeriose/microbiologia , Masculino , Produtos da Carne/economia , Medição de Risco , Perus
4.
J Microbiol ; 59(8): 771-781, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34061343

RESUMO

Listeria monocytogenes is a food-borne pathogen responsible for neurolisteriosis, which is potentially lethal in immunocompromised individuals. Microglia are the main target cells for L. monocytogenes in central nervous system (CNS). However, the precise mechanisms by which they trigger neuroinflammatory processes remain unknown. The BV2 microglial cell line and a murine model of L. monocytogenes infection were used for experiments in this study. Listeria monocytogenes induced pyroptosis and nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome activation in BV2. Pharmacological inhibition of the NLRP3 inflammasome attenuated L. monocytogenes-induced pyroptosis. Moreover, inhibition of nuclear factor kappa-B (NF-κB) and extracellular regulated protein kinases (ERK) pathways induced a decrease in caspase1 activation and mature IL-1ß-17 secretion. Our collective findings support critical involvement of the NLRP3 inflammasome in L. monocytogenes-induced neuroinflammation and, to an extent, ROS production. In addition, ERK and NF-κB signaling play an important role in activation of the NLRP3 inflammasome, both in vitro and in vivo.


Assuntos
Inflamassomos/imunologia , Listeria monocytogenes/fisiologia , Listeriose/imunologia , Microglia/microbiologia , NF-kappa B/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Espécies Reativas de Oxigênio/imunologia , Animais , Humanos , Inflamassomos/genética , Listeria monocytogenes/genética , Listeriose/genética , Listeriose/microbiologia , Listeriose/fisiopatologia , Sistema de Sinalização das MAP Quinases , Camundongos , Microglia/citologia , Microglia/imunologia , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Piroptose , Transdução de Sinais
5.
BMC Infect Dis ; 21(1): 564, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118865

RESUMO

BACKGROUND: Listeria monocytogenes (LM) has come to be a major public health issue of at-risk groups, causing high morbidity and mortality. Despite this data, studies are very limited in developing countries like Ethiopia. Thus, we aimed to isolate and characterize LM in terms of antibiogram and biofilm formation among pregnant women with fever, women with a history of spontaneous abortion, women with a history of fetal loss, and women with preterm delivery at Jimma University Medical Center (JUMC), southwest Ethiopia. METHODS: A cross-sectional study was done among 144 women from June to August 2019. Isolates were tested for antibiotic susceptibility and biofilm formation using disc diffusion and microtiter plate method, respectively. Data were collected using a structured questionnaire, entered into Epidata 3.1 and logistic regression was done by SPSS v25.0. RESULTS: LM was isolated in 8 (5.56%) of 144 screened women. The isolation rate of LM was relatively higher among women with a history of fetal loss (9.7%), followed by women with preterm delivery (6.25%). One of the six cord blood was positive for LM, indicating that the transplacental transmission rate at JUMC was 16.7%. More than 2% of women with an ongoing pregnancy were found to have LM septicemia, which could hurt their fetus. All of the isolates tested were susceptible to Ampicillin. However, all of the isolates were resistant to Penicillin and Meropenem and were biofilm producers. CONCLUSIONS: The high magnitude of pregnancy-related listeriosis in the current study setting appears that implementation of educational programs targeting risk reduction and more studies to identify sources of LM are warranted. The choice of antibiotics should be after susceptibility testing.


Assuntos
Antibacterianos/farmacologia , Listeria monocytogenes , Listeriose/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Centros Médicos Acadêmicos , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/isolamento & purificação , Listeriose/prevenção & controle , Testes de Sensibilidade Microbiana , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle
6.
Front Immunol ; 12: 667664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135896

RESUMO

The yellow mealworm beetle (Tenebrio molitor) has been exploited as an experimental model to unravel the intricacies of cellular and humoral immunity against pathogenic infections. Studies on this insect model have provided valuable insights into the phenotypic plasticity of immune defenses against parasites and pathogens. It has thus been possible to characterize the hemocoelic defenses of T. molitor that rely on the recognition of non-self-components of pathogens by pattern recognition receptors (PRRs). The subsequent signaling cascade activating pathways such as the NF-κB controlled by Toll and IMD pathways lead to the synthesis of antimicrobial peptides (AMPs), onset of hemocyte-driven phagocytosis, and activation of the prophenoloxidase cascade regulating the process of melanization. Nevertheless, the activation of autophagy-mediated defenses of T. molitor against the facultative intracellular gram-positive bacterium Listeria monocytogenes provides clear evidence of the existence of a cross-talk between autophagy and the IMD pathway. Moreover, the identification of several autophagy-related genes (Atgs) in T. molitor transcriptome and expressed sequence tag (EST) databases has contributed to the understanding of the autophagy-signaling cascade triggered by L. monocytogenes challenge. Providing further evidence of the cross-talk hypothesis, TmRelish has been shown to be required not only for regulating the synthesis of AMPs through the PGRP-LE/IMD pathway activation but also for the expression of Atgs in T. molitor larvae following L. monocytogenes challenge. Notably, L. monocytogenes can stimulate the T. molitor innate immune system by producing molecules recognized by the multifunctional PRR (TmPGRP-LE), which stimulates intracellular activation of the IMD pathway and autophagy. Considering the conservation of autophagy components involved in combating intracellular pathogens, it will be interesting to extrapolate a dynamic cross-talk model of immune activation. This review summarizes the most significant findings on the regulation of autophagy in T. molitor during L. monocytogenes infection and on the role of the innate immunity machinery, including the NF-κB pathway, in the control of pathogenic load.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Imunidade Inata , Proteínas de Insetos/metabolismo , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Macroautofagia , Tenebrio/microbiologia , Animais , Proteínas Relacionadas à Autofagia/genética , Carga Bacteriana , Interações Hospedeiro-Patógeno , Proteínas de Insetos/genética , Listeria monocytogenes/imunologia , Listeriose/genética , Listeriose/imunologia , Listeriose/metabolismo , Transdução de Sinais , Tenebrio/genética , Tenebrio/imunologia , Tenebrio/metabolismo
7.
Sci Rep ; 11(1): 12195, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108547

RESUMO

Listeria monocytogenes is a ubiquitous bacterium capable of colonising and persisting within food production environments (FPEs) for many years, even decades. This ability to colonise, survive and persist within the FPEs can result in food product cross-contamination, including vulnerable products such as ready to eat food items. Various environmental and genetic elements are purported to be involved, with the ability to form biofilms being an important factor. In this study we examined various mechanisms which can influence colonisation in FPEs. The ability of isolates (n = 52) to attach and grow in biofilm was assessed, distinguishing slower biofilm formers from isolates forming biofilm more rapidly. These isolates were further assessed to determine if growth rate, exopolymeric substance production and/or the agr signalling propeptide influenced these dynamics and could promote persistence in conditions reflective of FPE. Despite no strong association with the above factors to a rapid colonisation phenotype, the global transcriptome suggested transport, energy production and metabolism genes were widely upregulated during the initial colonisation stages under nutrient limited conditions. However, the upregulation of the metabolism systems varied between isolates supporting the idea that L. monocytogenes ability to colonise the FPEs is strain-specific.


Assuntos
Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Indústria de Processamento de Alimentos/normas , Listeria monocytogenes/fisiologia , Listeriose/microbiologia , Proteínas de Bactérias/genética , Monitoramento Ambiental , Listeria monocytogenes/classificação , Listeria monocytogenes/isolamento & purificação , Listeriose/transmissão , Transcriptoma , Fatores de Virulência
8.
Biomolecules ; 11(5)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946460

RESUMO

Formulations with lactate as an antimicrobial and high-pressure processing (HPP) as a lethal treatment are combined strategies used to control L. monocytogenes in cooked meat products. Previous studies have shown that when HPP is applied in products with lactate, the inactivation of L. monocytogenes is lower than that without lactate. The purpose of the present work was to identify the molecular mechanisms underlying the piezo-protection effect of lactate. Two L. monocytogenes strains (CTC1034 and EGDe) were independently inoculated in a cooked ham model medium without and with 2.8% potassium lactate. Samples were pressurized at 400 MPa for 10 min at 10 °C. Samples were subjected to RNA extraction, and a shotgun transcriptome sequencing was performed. The short exposure of L. monocytogenes cells to lactate through its inoculation in a cooked ham model with lactate 1h before HPP promoted a shift in the pathogen's central metabolism, favoring the metabolism of propanediol and ethanolamine together with the synthesis of the B12 cofactor. Moreover, the results suggest an activated methyl cycle that would promote modifications in membrane properties resulting in an enhanced resistance of the pathogen to HPP. This study provides insights on the mechanisms developed by L. monocytogenes in response to lactate and/or HPP and sheds light on the understanding of the piezo-protective effect of lactate.


Assuntos
Membrana Externa Bacteriana/efeitos dos fármacos , Ácidos Graxos/metabolismo , Ácido Láctico/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/metabolismo , Produtos da Carne/microbiologia , Animais , Antibacterianos/farmacologia , DNA Bacteriano , Etanolamina/metabolismo , Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Indústria de Processamento de Alimentos/métodos , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Listeria monocytogenes/genética , Listeriose/microbiologia , Membranas/efeitos dos fármacos , Redes e Vias Metabólicas , Pressão , Propilenoglicóis/metabolismo , Suínos , Temperatura , Fatores de Tempo , Vitamina B 12/biossíntese
9.
Anal Bioanal Chem ; 413(16): 4161-4180, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34041576

RESUMO

Listeria monocytogenes is an invasive opportunistic foodborne pathogen and its routine surveillance is critical for protecting the food supply and public health. The traditional detection methods are time-consuming and require trained personnel. Lateral flow immunoassay (LFIA), on the other hand, is an easy-to-perform, rapid point-of-care test and has been widely used as an inexpensive surveillance tool. In recent times, nucleic acid-based lateral flow immunoassays (NALFIA) are also developed to improve sensitivity and specificity. A significant improvement in lateral flow-based assays has been reported in recent years, especially the ligands (antibodies, nucleic acids, aptamers, bacteriophage), labeling molecules, and overall assay configurations to improve detection sensitivity, specificity, and automated interpretation of results. In most commercial applications, LFIA has been used with enriched food/environmental samples to ensure detection of live cells thus prolonging the assay time to 24-48 h; however, with the recent improvement in LFIA sensitivity, results can be obtained in less than 8 h with shortened and improved enrichment practices. Incorporation of surface-enhanced Raman spectroscopy and/or immunomagnetic separation could significantly improve LFIA sensitivity for near-real-time point-of-care detection of L. monocytogenes for food safety and public health applications.


Assuntos
Imunoensaio/métodos , Listeria monocytogenes/isolamento & purificação , Listeriose/microbiologia , Animais , Anticorpos Imobilizados/química , Microbiologia de Alimentos , Humanos , Imunoensaio/instrumentação , Listeriose/diagnóstico , Ácidos Nucleicos/química , Sistemas Automatizados de Assistência Junto ao Leito
10.
Nat Immunol ; 22(6): 699-710, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34040226

RESUMO

It is increasingly recognized that immune development within mucosal tissues is under the control of environmental factors during early life. However, the cellular mechanisms that underlie such temporally and regionally restrictive governance of these processes are unclear. Here, we uncover an extrathymic pathway of immune development within the colon that is controlled by embryonic but not bone marrow-derived macrophages, which determines the ability of these organs to receive invariant natural killer T (iNKT) cells and allow them to establish local residency. Consequently, early-life perturbations of fetal-derived macrophages result in persistent decreases of mucosal iNKT cells and is associated with later-life susceptibility or resistance to iNKT cell-associated mucosal disorders. These studies uncover a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota, and they reveal an important postnatal function of macrophages that emerge in fetal life.


Assuntos
Colite/imunologia , Mucosa Intestinal/imunologia , Listeriose/imunologia , Macrófagos/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Animais , Proliferação de Células/genética , Colite/microbiologia , Colite/patologia , Colo/citologia , Colo/embriologia , Colo/imunologia , Colo/patologia , Citocinas/metabolismo , Toxina Diftérica/administração & dosagem , Toxina Diftérica/imunologia , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Vida Livre de Germes , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/embriologia , Mucosa Intestinal/patologia , Listeriose/microbiologia , Listeriose/patologia , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , RNA-Seq , Transdução de Sinais/genética , Transdução de Sinais/imunologia
11.
Front Immunol ; 12: 672353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995413

RESUMO

Invasive foodborne Listeria monocytogenes infection causes gastroenteritis, septicemia, meningitis, and chorioamnionitis, and is associated with high case-fatality rates in the elderly. It is unclear how aging alters gut microbiota, increases risk of listeriosis, and causes dysbiosis post-infection. We used a geriatric murine model of listeriosis as human surrogate of listeriosis for aging individuals to study the effect of aging and L. monocytogenes infection. Aging and listeriosis-induced perturbation of gut microbiota and disease severity were compared between young-adult and old mice. Young-adult and old mice were dosed intragastrically with L. monocytogenes. Fecal pellets were collected pre- and post-infection for microbiome analysis. Infected old mice had higher Listeria colonization in liver, spleen, and feces. Metagenomics analyses of fecal DNA-sequences showed increase in α-diversity as mice aged, and infection reduced its diversity. The relative abundance of major bacterial phylum like, Bacteroidetes and Firmicutes remained stable over aging or infection, while the Verrucomicrobia phylum was significantly reduced only in infected old mice. Old mice showed a marked reduction in Clostridaiceae and Lactobacillaceae bacteria even before infection when compared to uninfected young-adult mice. L. monocytogenes infection increased the abundance of Porphyromonadaceae and Prevotellaceae in young-adult mice, while members of the Ruminococcaceae and Lachnospiraceae family were significantly increased in old mice. The abundance of the genera Blautia and Alistipes were significantly reduced post-infection in young-adult and in old mice as compared to their uninfected counterparts. Butyrate producing, immune-modulating bacterial species, like Pseudoflavonifractor and Faecalibacterium were significantly increased only in old infected mice, correlating with increased intestinal inflammatory mRNA up-regulation from old mice tissue. Histologic analyses of gastric tissues showed extensive lesions in the Listeria-infected old mice, more so in the non-glandular region and fundus than in the pylorus. Commensal species like Lactobacillus, Clostridiales, and Akkermansia were only abundant in infected young-adult mice but their abundance diminished in the infected old mice. Listeriosis in old mice enhances the abundance of butyrate-producing inflammatory members of the Ruminococcaceae/Lachnospiraceae bacteria while reducing/eliminating beneficial commensals in the gut. Results of this study indicate that, aging may affect the composition of gut microbiota and increase the risk of invasive L. monocytogenes infection.


Assuntos
Envelhecimento/fisiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Listeriose/microbiologia , Animais , Feminino , Listeria monocytogenes , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Risco
12.
Sci Rep ; 11(1): 9066, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907261

RESUMO

Listeria monocytogenes is an opportunistic pathogen that is widely distributed in the environment. The aquatic environment may represent a potential source for the transmission of L. monocytogenes to animals and the food chain. The present study assessed the occurrence of L. monocytogenes in 191 surface water samples from rivers, streams and inland canals throughout Switzerland. Twenty-five (13%) of the surface water samples contained L. monocytogenes. Whole genome sequence (WGS) data were used to characterize the 25 isolates. The isolates belonged to major lineages I and II, with the majority assigned to either serotype 1/2a (48%), or 4b (44%). The predominant CCs identified were the hypervirulent serotype 4b clones CC1 and CC4, and the serotype CC412; all three have been implicated in listeriosis outbreaks and sporadic cases of human and animal infection worldwide. Two (8%) of the isolates belonged to CC6 which is an emerging hypervirulent clone. All isolates contained intact genes associated with invasion and infection, including inlA/B and prfA. The four CC4 isolates all harbored Listeria pathogenicity island 4 (LIPI-4), which confers hypervirulence. The occurrence of L. monocytogenes in river ecosystems may contribute to the dissemination and introduction of clinically highly relevant strains to the food chain.


Assuntos
Proteínas de Bactérias/genética , Ecossistema , Genoma Bacteriano , Ilhas Genômicas , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Animais , Variação Genética , Genótipo , Listeriose/genética , Suíça , Sequenciamento Completo do Genoma
13.
Infect Immun ; 89(7): e0076820, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33782151

RESUMO

The development of T cell-based subunit protein vaccines against diseases such as tuberculosis and malaria remains a challenge for immunologists. Here, we have identified a nanoemulsion adjuvant, Adjuplex (ADJ), which enhanced dendritic cell (DC) cross-presentation and elicited effective memory T cell-based immunity to Listeria monocytogenes. We further evaluated whether cross-presentation induced by ADJ can be combined with the immunomodulatory effects of Toll-like receptor (TLR) agonists (CpG or glucopyranosyl lipid adjuvant [GLA]) to evoke systemic CD8 T cell-based immunity to L. monocytogenes. Mechanistically, vaccination with ADJ, alone or in combination with CpG or GLA, augmented activation and antigen uptake by CD103+ migratory and CD8α+ resident DCs and upregulated CD69 expression on B and T lymphocytes in vaccine-draining lymph nodes. By engaging basic leucine zipper ATF-like transcription factor 3-dependent cross-presenting DCs, ADJ potently elicited effector CD8 T cells that differentiated into granzyme B-expressing CD27LO effector-like memory CD8 T cells, which provided effective immunity to L. monocytogenes in the spleen and liver. CpG or GLA alone did not elicit effector-like memory CD8 T cells and induced moderate protection in the spleen but not in the liver. Surprisingly, combining CpG or GLA with ADJ reduced the number of ADJ-induced memory CD8 T cells and compromised protective immunity to L. monocytogenes, especially in the liver. Taken together, the data presented in this study provide a glimpse of protective CD8 T cell memory differentiation induced by a nanoemulsion adjuvant and demonstrate the unexpected negative effects of TLR signaling on the magnitude of CD8 T cell memory and protective immunity to L. monocytogenes, a model intracellular pathogen.


Assuntos
Adjuvantes Imunológicos , Linfócitos T CD8-Positivos/imunologia , Interações Hospedeiro-Patógeno/imunologia , Memória Imunológica , Listeria/imunologia , Listeriose/imunologia , Listeriose/microbiologia , Biomarcadores , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/imunologia , Imunomodulação , Imunofenotipagem , Listeriose/metabolismo , Transdução de Sinais
14.
Immunity ; 54(4): 829-844.e5, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33705706

RESUMO

Memory T cells are thought to rely on oxidative phosphorylation and short-lived effector T cells on glycolysis. Here, we investigated how T cells arrive at these states during an immune response. To understand the metabolic state of rare, early-activated T cells, we adapted mass cytometry to quantify metabolic regulators at single-cell resolution in parallel with cell signaling, proliferation, and effector function. We interrogated CD8+ T cell activation in vitro and in response to Listeria monocytogenes infection in vivo. This approach revealed a distinct metabolic state in early-activated T cells characterized by maximal expression of glycolytic and oxidative metabolic proteins. Cells in this transient state were most abundant 5 days post-infection before rapidly decreasing metabolic protein expression. Analogous findings were observed in chimeric antigen receptor (CAR) T cells interrogated longitudinally in advanced lymphoma patients. Our study demonstrates the utility of single-cell metabolic analysis by mass cytometry to identify metabolic adaptations of immune cell populations in vivo and provides a resource for investigations of metabolic regulation of immune responses across a variety of applications.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Ativação Linfocitária/imunologia , Transdução de Sinais/imunologia , Animais , Proliferação de Células/fisiologia , Feminino , Glicólise/imunologia , Memória Imunológica/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Listeriose/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosforilação Oxidativa , Receptores de Antígenos Quiméricos/imunologia , Análise de Célula Única/métodos
15.
Vasc Endovascular Surg ; 55(7): 744-748, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33736558

RESUMO

Primary aortitis (PA) secondary to Listeria monocytogenes is extremely rare with only a few cases reported in the literature. Presently, there is no consensus concerning the best treatment when no complications are found in the thoracic computed tomography (CT) imaging. This report illustrates the clinical presentation and favorable clinical course of a rare case of PA secondary to Listeria monocytogenes in an 82-year-old diabetic woman, successfully treated with conservative management with 18 months of follow up. Included in this article, we additionally present a review of the literature of this uncommon etiology of infectious aortitis.


Assuntos
Antibacterianos/uso terapêutico , Aortite/tratamento farmacológico , Tratamento Conservador , Listeria monocytogenes/isolamento & purificação , Listeriose/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Aortite/diagnóstico , Aortite/microbiologia , Feminino , Humanos , Listeriose/diagnóstico , Listeriose/microbiologia , Resultado do Tratamento
16.
PLoS One ; 16(2): e0242297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33630832

RESUMO

We performed whole-genome multi-locus sequence typing for 2554 genes in a large and heterogenous panel of 180 Listeria monocytogenes strains having diverse geographical and temporal origins. The subtyping data was used for characterizing genetic variation and evaluating patterns of linkage disequilibrium in the pan-genome of L. monocytogenes. Our analysis revealed the presence of strong linkage disequilibrium in L. monocytogenes, with ~99% of genes showing significant non-random associations with a large majority of other genes in the genome. Twenty-seven loci having lower levels of association with other genes were considered to be potential "hot spots" for horizontal gene transfer (i.e., recombination via conjugation, transduction, and/or transformation). The patterns of linkage disequilibrium in L. monocytogenes suggest limited exchange of foreign genetic material in the genome and can be used as a tool for identifying new recombinant strains. This can help understand processes contributing to the diversification and evolution of this pathogenic bacteria, thereby facilitating development of effective control measures.


Assuntos
Genoma Bacteriano , Desequilíbrio de Ligação , Listeria monocytogenes/genética , Listeriose/microbiologia , Microbiologia de Alimentos , Variação Genética , Humanos , Listeria monocytogenes/isolamento & purificação , Tipagem de Sequências Multilocus , Filogenia
17.
Nature ; 590(7846): 457-462, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33568812

RESUMO

In contrast to nearly all other tissues, the anatomy of cell differentiation in the bone marrow remains unknown. This is owing to a lack of strategies for examining myelopoiesis-the differentiation of myeloid progenitors into a large variety of innate immune cells-in situ in the bone marrow. Such strategies are required to understand differentiation and lineage-commitment decisions, and to define how spatial organizing cues inform tissue function. Here we develop approaches for imaging myelopoiesis in mice, and generate atlases showing the differentiation of granulocytes, monocytes and dendritic cells. The generation of granulocytes and dendritic cells-monocytes localizes to different blood-vessel structures known as sinusoids, and displays lineage-specific spatial and clonal architectures. Acute systemic infection with Listeria monocytogenes induces lineage-specific progenitor clusters to undergo increased self-renewal of progenitors, but the different lineages remain spatially separated. Monocyte-dendritic cell progenitors (MDPs) map with nonclassical monocytes and conventional dendritic cells; these localize to a subset of blood vessels expressing a major regulator of myelopoiesis, colony-stimulating factor 1 (CSF1, also known as M-CSF)1. Specific deletion of Csf1 in endothelium disrupts the architecture around MDPs and their localization to sinusoids. Subsequently, there are fewer MDPs and their ability to differentiate is reduced, leading to a loss of nonclassical monocytes and dendritic cells during both homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood cell differentiation.


Assuntos
Rastreamento de Células/métodos , Células Mieloides/citologia , Mielopoese , Coloração e Rotulagem/métodos , Animais , Atlas como Assunto , Vasos Sanguíneos/citologia , Vasos Sanguíneos/metabolismo , Linhagem da Célula , Autorrenovação Celular , Células Dendríticas/citologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Granulócitos/citologia , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Fator Estimulador de Colônias de Macrófagos/deficiência , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Masculino , Camundongos , Monócitos/citologia , Células Mieloides/metabolismo
18.
NPJ Biofilms Microbiomes ; 7(1): 18, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558519

RESUMO

Environmental cues promote microbial biofilm formation and physiological and genetic heterogeneity. In food production facilities, biofilms produced by pathogens are a major source for food contamination; however, the pathogenesis of biofilm-isolated sessile cells is not well understood. We investigated the pathogenesis of sessile Listeria monocytogenes (Lm) using cell culture and mouse models. Lm sessile cells express reduced levels of the lap, inlA, hly, prfA, and sigB and show reduced adhesion, invasion, translocation, and cytotoxicity in the cell culture model than the planktonic cells. Oral challenge of C57BL/6 mice with food, clinical, or murinized-InlA (InlAm) strains reveals that at 12 and 24 h post-infection (hpi), Lm burdens are lower in tissues of mice infected with sessile cells than those infected with planktonic cells. However, these differences are negligible at 48 hpi. Besides, the expressions of inlA and lap mRNA in sessile Lm from intestinal content are about 6.0- and 280-fold higher than the sessle inoculum, respectively, suggesting sessile Lm can still upregulate virulence genes shortly after ingestion (12 h). Similarly, exposure to simulated gastric fluid (SGF, pH 3) and intestinal fluid (SIF, pH 7) for 13 h shows equal reduction in sessile and planktonic cell counts, but induces LAP and InlA expression and pathogenic phenotypes. Our data show that the virulence of biofilm-isolated Lm is temporarily attenuated and can be upregulated in mice during the early stage (12-24 hpi) but fully restored at a later stage (48 hpi) of infection. Our study further demonstrates that in vitro cell culture assay is unreliable; therefore, an animal model is essential for studying the pathogenesis of biofilm-isolated bacteria.


Assuntos
Biofilmes/crescimento & desenvolvimento , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Fatores de Virulência/genética , Animais , Aderência Bacteriana , Proteínas de Bactérias/genética , Células CACO-2 , Modelos Animais de Doenças , Feminino , Microbiologia de Alimentos , Regulação Bacteriana da Expressão Gênica , Humanos , Listeria monocytogenes/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
Dev Cell ; 56(4): 443-460.e11, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33621492

RESUMO

Intracellular pathogens alter their host cells' mechanics to promote dissemination through tissues. Conversely, host cells may respond to the presence of pathogens by altering their mechanics to limit infection. Here, we monitored epithelial cell monolayers infected with intracellular bacterial pathogens, Listeria monocytogenes or Rickettsia parkeri, over days. Under conditions in which these pathogens trigger innate immune signaling through NF-κB and use actin-based motility to spread non-lytically intercellularly, we found that infected cell domains formed three-dimensional mounds. These mounds resulted from uninfected cells moving toward the infection site, collectively squeezing the softer and less contractile infected cells upward and ejecting them from the monolayer. Bacteria in mounds were less able to spread laterally in the monolayer, limiting the growth of the infection focus, while extruded infected cells underwent cell death. Thus, the coordinated forceful action of uninfected cells actively eliminates large domains of infected cells, consistent with this collective cell response representing an innate immunity-driven process.


Assuntos
Competição entre as Células , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Imunidade Inata , Listeria monocytogenes/fisiologia , Listeriose/imunologia , Listeriose/microbiologia , Transdução de Sinais , Actomiosina/metabolismo , Animais , Apoptose , Fenômenos Biomecânicos , Adesão Celular , Linhagem Celular , Simulação por Computador , Cães , Interações Hospedeiro-Patógeno , Humanos , Junções Intercelulares/metabolismo , Terapia a Laser , Listeriose/genética , Células Madin Darby de Rim Canino , NF-kappa B/metabolismo , Imagem com Lapso de Tempo , Transcrição Genética
20.
Ecotoxicol Environ Saf ; 213: 112065, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636464

RESUMO

Listeria monocytogenes widely exists in the natural environment and does great harm, which can cause worldwide public safety problem. Infection with L. monocytogenes can cause rapid death of Kupffer cell (KCs) in liver tissue and liver damage. American ginseng saponins is a natural compound in plants, which has great potential in inhibiting L. monocytogenes infection. Therefore, American ginseng stem-leaf saponins (AGS) and American ginseng heat-transformed saponins (HTS) were used as raw materials to study their bacteriostatic experiments in vivo and in vitro. In this experiment, female Kunming mice were randomly divided into five groups: control group, negative group, AGS group, HTS group (10 mg/kg/day in an equal volume via gastric administration) and penicillin group, each group containing six mice. Profiles AGS and HTS components were evaluated by high-performance liquid chromatography (HPLC) analysis. The bacteriostatic effect of AGS and HTS on L. monocytogenes was evaluated by inhibition zone test, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The bacteriostatic effect of AGS and HTS pretreatment on mice infected with L. monocytogenes were studies by animal experimental. The results showed that the content of polar saponins in AGS was 0.81 ± 0.003 mg/mg, less polar saponins was 0.08 ± 0.02 mg/mg, the content of polar saponins in HTS was 0.10 ± 0.01 mg/mg, less polar saponins was 0.76 ± 0.02 mg/mg. The in vitro bacteriostatic diameter of HTS (16.6 ± 0.8 mm) is large than that of AGS (10.2 ± 1.2 mm). AGS and HTS pretreatment could reduce the colony numbers in the livers of mice infected with Listeria monocytogenes. The levels of alanine aminotransferase (ALT), IL-1ß, IL-6, TNF-α and IFN-γ in the livers of mice in the pretreatment group were significantly lower than those in the negative group. There were obvious leukoplakia, calcification and other liver damage on the liver surface in the negative control group, and obvious inflammatory cell infiltration in HE sections. AGS and HTS pretreatment can reduce liver injury caused by L. monocytogenes and protect the liver. Compared with AGS, HTS has higher content of less polar saponins and better bacteriostatic effect in vitro. The count of bacterial in liver tissue of HTS group was significantly lower, the survival rate was significantly higher than that of AGS group. Less polar saponins had better bacteriostatic effect. Collectively, less polar saponins pretreatment has a protective effect on mice infected with L. monocytogenes, to which alleviated liver damage, improved anti-inflammatory ability and immunity of the body, protected liver may contribute.


Assuntos
Ginsenosídeos/toxicidade , Listeria monocytogenes/efeitos dos fármacos , Animais , Feminino , Listeriose/imunologia , Listeriose/metabolismo , Listeriose/microbiologia , Listeriose/veterinária , Fígado/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estômago , Fator de Necrose Tumoral alfa
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