Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.626
Filtrar
1.
BMJ Case Rep ; 15(5)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523512

RESUMO

Listeria monocytogenes is a foodborne pathogen, typically associated with contaminated dairy products and deli meats. L. monocytogenes can lead to severe infections in high-risk patient populations; in neonates, listeriosis is rare but carries a high rate of neurological morbidity and mortality. Here a case of neonatal listeriosis, in the newborn of a young Hispanic mother who frequently ate queso fresco (a fresh Mexican cheese), is presented. Pregnant women are commonly counselled to avoid unpasteurised dairy during the pregnancy, but many are unaware that soft cheeses, and other food products, may pose risks for perinatal infection. L. monocytogenes remains a cause of food-related outbreaks and maternal and neonatal sepsis around the world, and healthcare providers should ensure that expectant mothers are carefully counselled regarding potential sources.


Assuntos
Queijo , Doenças Fetais , Doenças do Recém-Nascido , Listeria monocytogenes , Listeriose , Surtos de Doenças , Feminino , Microbiologia de Alimentos , Humanos , Recém-Nascido , Listeriose/diagnóstico , Listeriose/tratamento farmacológico , Gravidez
2.
PLoS One ; 17(5): e0267972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35533187

RESUMO

Listeria monocytogenes can cause listeriosis, and people with hypoimmunity such as pregnant women, infants and fetuses are at high risk of invasive infection. Although the incidence of listeriosis is low, the fatality rate is high. Therefore, continual surveillance and rapid epidemiological investigation are crucial for addressing L. monocytogenes. Because of the popularity of next-generation sequencing, obtaining the whole-genome sequence of a bacterium is easy. Several genome-based typing methods are available, and core-genome multilocus sequence typing (cgMLST) is the most recognized methods. Using cgMLST typing to compare L. monocytogenes whole-genome sequences (WGS) with those obtained across distinct regions is beneficial. However, the concern is how to incorporate the powerful cgMLST method into investigations, such as by using source tracing. Herein, we present an easy-to-use web service called-LmTraceMap (http://lmtracemap.cgu.edu.tw/hua_map/test/upload.php; http://120.126.17.192/hua_map/test/upload.php) that can help public-health professionals rapidly trace closely related isolates worldwide and visually inspect them in search results on a world map with labeled epidemiological data. We expect the proposed service to improve the convenience of public health investigations.


Assuntos
Listeria monocytogenes , Listeriose , Feminino , Microbiologia de Alimentos , Genoma Bacteriano , Humanos , Listeria monocytogenes/genética , Listeriose/epidemiologia , Listeriose/microbiologia , Tipagem de Sequências Multilocus/métodos , Gravidez , Sequenciamento Completo do Genoma/métodos
3.
Front Cell Infect Microbiol ; 12: 793335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402308

RESUMO

Listeria monocytogenes, as a model organism, is a causative agent of enteric pathogen that causes systemic infection. However, the interaction of L. monocytogenes and small intestinal epithelium has not been fully elucidated yet. In this study, mice and intestinal organoids were chosen as the models to investigate the influence of L. monocytogenes infection on the intestinal secretory cells and its differentiation-related pathways. Results confirmed the phenomenon of intestinal damage that L. monocytogenes infection could lead to villi damage in mice, which was accompanied by the increase of TNF-α production in jejunum as well as lipopolysaccharide (LPS) secretion in serum. Moreover, it was demonstrated that L. monocytogenes infection increased the number of goblet and Paneth cells in mice and intestinal organoids and upregulated the expression of Muc2 and Lyz. Furthermore, L. monocytogenes decreased the relative expression of Notch pathway-related genes (Jag1, Dll4, Notch1, and Hes1) while upregulating the relative expression of Math1 gene in mice and intestinal organoids. This indicated that L. monocytogenes infection caused the inhibition of Notch pathway, which may be the reason for the increased number of goblet and Paneth cells in the intestine. Collectively, these results are expected to provide more information on the mechanism of L. monocytogenes infection in the intestine.


Assuntos
Listeria monocytogenes , Listeriose , Animais , Mucosa Intestinal/metabolismo , Intestino Delgado , Intestinos , Listeriose/metabolismo , Camundongos
4.
Front Cell Infect Microbiol ; 12: 849915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372114

RESUMO

Many bacterial species, including several pathogens, can enter a so-called "viable but non-culturable" (VBNC) state when subjected to stress. Bacteria in the VBNC state are metabolically active but have lost their ability to grow on standard culture media, which compromises their detection by conventional techniques based on bacterial division. Under certain conditions, VBNC bacteria can regain their growth capacity and, for pathogens, their virulence potential, through a process called resuscitation. Here, we review the current state of knowledge of the VBNC state of Listeria monocytogenes (Lm), a Gram-positive pathogenic bacterium responsible for listeriosis, one of the most dangerous foodborne zoonosis. After a brief summary of characteristics of VBNC bacteria, we highlight work on VBNC Lm in the environment and in agricultural and food industry settings, with particular emphasis on the impact of antimicrobial treatments. We subsequently discuss recent data suggesting that Lm can enter the VBNC state in the host, raising the possibility that VBNC forms contribute to the asymptomatic carriage of this pathogen in wildlife, livestock and even humans. We also consider the resuscitation and virulence potential of VBNC Lm and the danger posed by these bacteria to at-risk individuals, particularly pregnant women. Overall, we put forth the hypothesis that VBNC forms contribute to adaptation, persistence, and transmission of Lm between different ecological niches in the One-Health continuum, and suggest that screening for healthy carriers, using alternative techniques to culture-based enrichment methods, should better prevent listeriosis risks.


Assuntos
Listeria monocytogenes , Listeriose , Saúde Única , Animais , Feminino , Humanos , Listeriose/microbiologia , Gravidez , Virulência , Zoonoses
5.
Appl Environ Microbiol ; 88(8): e0035722, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35377164

RESUMO

A 5-year survey of public access surface waters in an agricultural region of the Central California Coast was done to assess the prevalence of the foodborne pathogen Listeria monocytogenes. In nature, L. monocytogenes lives as a saprophyte in soil and water, which are reservoirs for contamination of preharvest produce. Moore swabs were deployed biweekly in lakes, ponds, streams, and rivers during 2011 to 2016. L. monocytogenes was recovered in 1,224 of 2,922 samples, resulting in 41.9% prevalence. Multiple subtypes were isolated from 97 samples, resulting in 1,323 L. monocytogenes isolates. Prevalence was higher in winter and spring and after rain events in some waterways. Over 84% of the isolates were serotype 4b. Whole-genome sequencing was done on 1,248 isolates, and in silico multilocus sequence typing revealed 74 different sequence types (STs) and 39 clonal complexes (CCs). The clones most isolated, CC639, CC183, and CC1, made up 27%, 19%, and 13%, respectively, of the sequenced isolates. Other types were CC663, CC6, CC842, CC4, CC2, CC5, and CC217. All sequenced isolates contained intact copies of core L. monocytogenes virulence genes, and pathogenicity islands LIPI-3 and LIPI-4 were identified in 73% and 63%, respectively, of the sequenced isolates. The virulence factor internalin A was predicted to be intact in all but four isolates, while genes important for sanitizer and heavy metal resistance were found in <5% of the isolates. These waters are not used for crop irrigation directly, but they are available to wildlife and can flood fields during heavy rains. IMPORTANCE Listeria monocytogenes serotype 4b and 1/2a strains are implicated in most listeriosis, and hypervirulent listeriosis stems from strains containing pathogenicity islands LIPI-3 and LIPI-4. The waters and sediments in the Central California Coast agricultural region contain widespread and diverse L. monocytogenes populations, and all the isolates contain intact virulence genes. Emerging clones CC183 and CC639 were the most abundant clones, and major clones CC1, CC4, and CC6 were well represented. CC183 was responsible for three produce-related outbreaks in the last 7 years. Most of the isolates in the survey differ from those of lesser virulence that are often isolated from foods and food processing plants because they contain genes encoding an intact virulence factor, internalin A, and most did not contain genes for sanitizer and heavy metal resistance. This isolate collection is important for understanding L. monocytogenes populations in agricultural and natural regions.


Assuntos
Listeria monocytogenes , Listeriose , Humanos , Listeriose/epidemiologia , Tipagem de Sequências Multilocus , Prevalência , Fatores de Virulência/genética
6.
Sci Data ; 9(1): 190, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484273

RESUMO

Listeria monocytogenes (Lm) is a ubiquitous bacterium that causes listeriosis, a serious foodborne illness. In the nature-to-human transmission route, Lm can prosper in various ecological niches. Soil and decaying organic matter are its primary reservoirs. Certain clonal complexes (CCs) are over-represented in food production and represent a challenge to food safety. To gain new understanding of Lm adaptation mechanisms in food, the genetic background of strains found in animals and environment should be investigated in comparison to that of food strains. Twenty-one partners, including food, environment, veterinary and public health laboratories, constructed a dataset of 1484 genomes originating from Lm strains collected in 19 European countries. This dataset encompasses a large number of CCs occurring worldwide, covers many diverse habitats and is balanced between ecological compartments and geographic regions. The dataset presented here will contribute to improve our understanding of Lm ecology and should aid in the surveillance of Lm. This dataset provides a basis for the discovery of the genetic traits underlying Lm adaptation to different ecological niches.


Assuntos
Doenças Transmitidas por Alimentos , Listeria monocytogenes , Listeriose , Animais , Ecossistema , Doenças Transmitidas por Alimentos/microbiologia , Listeria monocytogenes/genética , Listeriose/epidemiologia , Listeriose/microbiologia
7.
Proc Natl Acad Sci U S A ; 119(10): e2113329119, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35239442

RESUMO

SignificanceThe CD4+ Treg response following acute Listeria infection is heterogeneous and deploys two distinct modes of suppression coinciding with initial pathogen exposure and resolution of infection. This bimodal suppression of CD8+ T cells during priming and contraction is mediated by separate Treg lineages. These findings make a significant contribution to our understanding of the functional plasticity inherent within Tregs, which allows these cells to serve as a sensitive and dynamic cellular rheostat for the immune system to prevent autoimmune pathology in the face of inflammation attendant to acute infection, enable expansion of the pathogen-specific response needed to control the infection, and reestablish immune homeostasis after the threat has been contained.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Linfócitos T Reguladores/imunologia , 5'-Nucleotidase/imunologia , Doença Aguda , Animais , Camundongos
8.
Nature ; 603(7903): 900-906, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35296858

RESUMO

Infections of the central nervous system are among the most serious infections1,2, but the mechanisms by which pathogens access the brain remain poorly understood. The model microorganism Listeria monocytogenes (Lm) is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest infections of the central nervous system3,4. Although immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known about the bacterial factors that underlie the neuroinvasion of Lm. Here we develop a clinically relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6 inoculated in a humanized mouse model of infection7, and we show that the bacterial surface protein InlB protects infected monocytes from Fas-mediated cell death by CD8+ T cells in a manner that depends on c-Met, PI3 kinase and FLIP. This blockade of specific anti-Lm cellular immune killing lengthens the lifespan of infected monocytes, and thereby favours the transfer of Lm from infected monocytes to the brain. The intracellular niche that is created by InlB-mediated cell-autonomous immune resistance also promotes Lm faecal shedding, which accounts for the selection of InlB as a core virulence gene of Lm. We have uncovered a specific mechanism by which a bacterial pathogen confers an increased lifespan to the cells it infects by rendering them resistant to cell-mediated immunity. This promotes the persistence of Lm within the host, its dissemination to the central nervous system and its transmission.


Assuntos
Doenças do Sistema Nervoso Central , Listeria monocytogenes , Listeriose , Animais , Proteínas de Bactérias/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Doenças do Sistema Nervoso Central/microbiologia , Modelos Animais de Doenças , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Camundongos , Monócitos , Virulência
9.
Fish Shellfish Immunol ; 123: 469-478, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35354104

RESUMO

Even though Listeria monocytogenes is an extensive-studied foodborne pathogen, genome analysis of isolates from snails that may represent a reservoir of L. monocytogenes are still scarce. Here, we use whole-genome sequencing (WGS) to assess the genomic diversity of hypervirulent, virulent and non-virulent phenotypes of 15 L. monocytogenes isolated from snails to unveil their survival, virulence, and host-pathogen mechanisms of interactions in a snail infection model. Most of isolates (66.7%) were characterized as multidrug resistant (MDR) and belonged to clonal complexes (CCs) which are strongly associated with cases of human infection. All isolates contained intact genes associated with invasion and infection while hypervirulent isolates are adapted to host environment, possessing genes which are involved in teichoic acid biosynthesis, peptidoglycan modification and biofilm formation, correlating with their tolerance to haemolymph plasma phenotype and biofilm formation ability. A snail infection model showed that hypervirulent isolates triggered programmed host cell death pathway by increasing up to 30% the circulating apoptotic hemocytes in combination with induced nitrate production and reactive oxygen species (ROS) generation in snails' haemolymph. In contrast, the administration of the non-virulent strain which possesses a truncated mogR gene that regulates flagellar motility gene expression led only to an increase of necrotic non-apoptotic cells. Overall, this study provides significant insights into the genetic diversity of L. monocytogenes from snails, the genomic features of them linked to their hypervirulent/non-virulent phenotype, and the mechanisms of host-pathogen interactions.


Assuntos
Listeria monocytogenes , Listeriose , Animais , Interações Hospedeiro-Patógeno , Carne , Sequenciamento Completo do Genoma
10.
Arch Microbiol ; 204(4): 201, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35239048

RESUMO

Listeriosis is an emerging bacterial disease of animals and humans worldwide, caused by Listeria monocytogenes. The infected dairy cows continuously shed the microbes in their milk, a human being's concern. This study was designed to molecular characterize the Listeria monocytogenes isolated from symptomatic cow's milk of tehsils Samundri, Gujar khan, and Alipur of Punjab. A total of 175 milk samples were collected, pre-enriched and cultured on PALCAM agar. The affirmation of the hlyA gene of Listeria monocytogenes was performed by polymerase chain reaction (PCR) and 3.43% of isolates were found positive. The phylogenetic analysis showed a resemblance of our isolates of Listeria monocytogenes with India (KP965733), the USA (DQ812484), and 3 of our isolates made a clade. The leucocytes and neutrophils count were found significantly increased in listeriosis affected cows. The Chi-square test showed a significant association between poor quality silage feeding and listeriosis. The presence of L.monocytogenes in cow's milk indicates a potential threat to humans. It is further recommended that it should be consistently monitored to ensure food safety.


Assuntos
Listeria monocytogenes , Listeriose , Animais , Bovinos , Feminino , Humanos , Listeria monocytogenes/genética , Listeriose/epidemiologia , Listeriose/microbiologia , Listeriose/veterinária , Leite/microbiologia , Paquistão , Filogenia
11.
BMJ Case Rep ; 15(2)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35228212

RESUMO

Current therapies frequently used for refractory septic shock include hydrocortisone, vasopressin, extracorporeal membrane oxygenation (ECMO) support, inodilators, levosimendan and methylene blue. The evidence for these treatments is very limited. We present a case of a 5-year-old patient with refractory septic shock, secondary to Listeria monocytogenes meningitis. She presented with status epilepticus and developed septic shock. Shock persisted despite multiple high-dose vasoactive medications. ECMO support was not available. The medical team decided to use methylene blue to revert the vasoplegia, with excellent results. Shortly after the administration, vasopressors were weaned off and the high lactate cleared. She developed severe neurological sequelae due to brain haemorrhage secondary to the Listeria meningitis. The evidence supporting methylene blue for refractory septic shock in paediatric patients is limited. This case represents the effectiveness of this therapy without secondary effects.


Assuntos
Oxigenação por Membrana Extracorpórea , Listeriose , Choque Séptico , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Listeriose/complicações , Listeriose/tratamento farmacológico , Azul de Metileno/uso terapêutico , Choque Séptico/complicações , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico
13.
Viruses ; 14(2)2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35215782

RESUMO

In this study, we examined the effect of a bacteriophage cocktail (tentatively designated as the Foodborne Outbreak Pill (FOP)) on the levels of Listeria monocytogenes in simulated small intestine, large intestine, and Caco-2 model systems. We found that FOP survival during simulated passage of the upper gastrointestinal was dependent on stomach pH, and that FOP robustly inhibited L. monocytogenes levels with effectiveness comparable to antibiotic treatment (ampicillin) under simulated ilium and colon conditions. The FOP did not inhibit the commensal bacteria, whereas ampicillin treatment led to dysbiosis-like conditions. The FOP was also more effective than an antibiotic in protecting Caco-2 cells from adhesion and invasion by L. monocytogenes (5-log reduction vs. 1-log reduction) while not triggering an inflammatory response. Our data suggested that the FOP may provide a robust protection against L. monocytogenes should the bacterium enter the human gastrointestinal tract (e.g., by consumption of contaminated food), without deleterious impact on the commensal bacteria.


Assuntos
Bacteriófagos/fisiologia , Microbioma Gastrointestinal , Listeria monocytogenes/virologia , Listeriose/terapia , Terapia por Fagos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Humanos , Intestinos/microbiologia , Listeria monocytogenes/fisiologia , Listeriose/microbiologia
14.
Appl Environ Microbiol ; 88(6): e0213621, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35108102

RESUMO

Listeria monocytogenes is a ubiquitous environmental bacterium associated with a wide variety of natural and human-made environments, such as soil, vegetation, livestock, food processing environments, and urban areas. It is also among the deadliest foodborne pathogens, and knowledge about its presence and diversity in potential sources is crucial to effectively track and control it in the food chain. Isolation of L. monocytogenes from various rural and urban environments showed higher prevalence in agricultural and urban developments than in forest or mountain areas, and that detection was positively associated with rainfall. Whole-genome sequencing (WGS) was performed for the collected isolates and for L. monocytogenes from Norwegian dairy farms and slugs (218 isolates in total). The data were compared to available data sets from clinical and food-associated sources in Norway collected within the last decade. Multiple examples of clusters of isolates with 0 to 8 whole-genome multilocus sequence typing (wgMLST) allelic differences were collected over time in the same location, demonstrating persistence of L. monocytogenes in natural, urban, and farm environments. Furthermore, several clusters with 6 to 20 wgMLST allelic differences containing isolates collected across different locations, times, and habitats were identified, including nine clusters harboring clinical isolates. The most ubiquitous clones found in soil and other natural and animal ecosystems (CC91, CC11, and CC37) were distinct from clones predominating among both clinical (CC7, CC121, and CC1) and food (CC9, CC121, CC7, and CC8) isolates. The analyses indicated that ST91 was more prevalent in Norway than other countries and revealed a high proportion of the hypovirulent ST121 among Norwegian clinical cases. IMPORTANCE Listeria monocytogenes is a deadly foodborne pathogen that is widespread in the environment. For effective management, both public health authorities and food producers need reliable tools for source tracking, surveillance, and risk assessment. For this, whole-genome sequencing (WGS) is regarded as the present and future gold standard. In the current study, we use WGS to show that L. monocytogenes can persist for months and years in natural, urban, and dairy farm environments. Notably, clusters of almost identical isolates, with genetic distances within the thresholds often suggested for defining an outbreak cluster, can be collected from geographically and temporally unrelated sources. The work highlights the need for a greater knowledge of the genetic relationships between clinical isolates and isolates of L. monocytogenes from a wide range of environments, including natural, urban, agricultural, livestock, food production, and food processing environments, to correctly interpret and use results from WGS analyses.


Assuntos
Listeria monocytogenes , Listeriose , Animais , Ecossistema , Fazendas , Microbiologia de Alimentos , Variação Genética , Listeriose/epidemiologia , Listeriose/microbiologia , Listeriose/veterinária , Sequenciamento Completo do Genoma
15.
Int J Mol Sci ; 23(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35216061

RESUMO

Listeria monocytogenes (Lm) bacterial ghosts (LMGs) were produced by the minimum inhibitory concentration (MIC) of HCl, H2SO4, and NaOH. Acid and alkali effects on the LMGs were compared by in vitro and in vivo analyses. Scanning electron microscope showed that all chemicals form lysis pores on the Lm cell envelopes. Real-time qPCR revealed a complete absence of genomic DNA in HCl- and H2SO4-induced LMGs but not in NaOH-induced LMGs. HCl-, H2SO4- and NaOH-induced LMGs showed weaker or missing protein bands on SDS-PAGE gel when compared to wild-type Lm. Murine macrophages exposed to the HCl-induced LMGs showed higher cell viability than those exposed to NaOH-induced LMGs or wild-type Lm. The maximum level of cytokine expression (TNF-α, iNOS, IFN-γ, and IL-10 mRNA) was observed in the macrophages exposed to NaOH-induced LMGs, while that of IL-1ß mRNA was observed in the macrophages exposed to HCl-induced LMGs. To investigate LMGs as a vaccine candidate, mice were divided into PBS buffer-injected, HCl- and NaOH-induced LMGs immunized groups. Mice vaccinated with HCl- and NOH-induced LMGs, respectively, significantly increased in specific IgG antibodies, bactericidal activities of serum, and CD4+ and CD8+ T-cell population. Antigenic Lm proteins reacted with antisera against HCl- and NOH-induced LMGs, respectively. Bacterial loads in HCl- and NaOH-induced LMGs immunized mice were significantly lower than PBS-injected mice after virulent Lm challenges. It suggested that vaccination with LMGs induces both humoral and cell-mediated immune responses and protects against virulent challenges.


Assuntos
Ácido Clorídrico/imunologia , Imunidade Celular/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Hidróxido de Sódio/imunologia , Vacinas/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Citocinas/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Ratos
16.
Immunity ; 55(3): 442-458.e8, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35182483

RESUMO

Consecutive exposures to different pathogens are highly prevalent and often alter the host immune response. However, it remains unknown how a secondary bacterial infection affects an ongoing adaptive immune response elicited against primary invading pathogens. We demonstrated that recruitment of Sca-1+ monocytes into lymphoid organs during Salmonella Typhimurium (STm) infection disrupted pre-existing germinal center (GC) reactions. GC responses induced by influenza, plasmodium, or commensals deteriorated following STm infection. GC disruption was independent of the direct bacterial interactions with B cells and instead was induced through recruitment of CCR2-dependent Sca-1+ monocytes into the lymphoid organs. GC collapse was associated with impaired cellular respiration and was dependent on TNFα and IFNγ, the latter of which was essential for Sca-1+ monocyte differentiation. Monocyte recruitment and GC disruption also occurred during LPS-supplemented vaccination and Listeria monocytogenes infection. Thus, systemic activation of the innate immune response upon severe bacterial infection is induced at the expense of antibody-mediated immunity.


Assuntos
Infecções Bacterianas , Listeriose , Linfócitos B , Centro Germinativo , Humanos , Monócitos
17.
Immunity ; 55(2): 254-271.e7, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35139352

RESUMO

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.


Assuntos
Inflamação/imunologia , Interferon gama/imunologia , Subpopulações de Linfócitos/imunologia , Células Th2/imunologia , Animais , Morte Celular/imunologia , Movimento Celular/imunologia , Hipersensibilidade/imunologia , Imunidade Inata , Interleucina-33/imunologia , Interleucina-5/metabolismo , Listeria monocytogenes , Listeriose/imunologia , Listeriose/mortalidade , Fígado/imunologia , Pulmão/imunologia , Subpopulações de Linfócitos/metabolismo , Lisofosfolipídeos/imunologia , Camundongos , Tecido Parenquimatoso/imunologia , Esfingosina/análogos & derivados , Esfingosina/imunologia , Células Th1/imunologia , Células Th2/metabolismo
18.
Science ; 375(6583): 859-863, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35201883

RESUMO

Group 3 innate lymphoid cells (ILC3s) are innate immune effectors that contribute to host defense. Whether ILC3 functions are stably modified after pathogen encounter is unknown. Here, we assess the impact of a time-restricted enterobacterial challenge to long-term ILC3 activation in mice. We found that intestinal ILC3s persist for months in an activated state after exposure to Citrobacter rodentium. Upon rechallenge, these "trained" ILC3s proliferate, display enhanced interleukin-22 (IL-22) responses, and have a superior capacity to control infection compared with naïve ILC3s. Metabolic changes occur in C. rodentium-exposed ILC3s, but only trained ILC3s have an enhanced proliferative capacity that contributes to increased IL-22 production. Accordingly, a limited encounter with a pathogen can promote durable phenotypic and functional changes in intestinal ILC3s that contribute to long-term mucosal defense.


Assuntos
Citrobacter rodentium/imunologia , Infecções por Enterobacteriaceae/imunologia , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Ativação Linfocitária , Linfócitos/imunologia , Imunidade Adaptativa , Animais , Proliferação de Células , Feminino , Imunidade Inata , Memória Imunológica , Interleucinas/metabolismo , Intestinos/imunologia , Listeria monocytogenes , Listeriose/imunologia , Linfócitos/metabolismo , Masculino , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos C57BL , Consumo de Oxigênio , RNA-Seq , Reinfecção/imunologia
19.
Microbiol Spectr ; 10(1): e0209521, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35196823

RESUMO

Listeria monocytogenes is a major pathogen contributing to foodborne outbreaks with high mortality. Nisin, a natural antimicrobial, has been widely used as a food preservative. However, the mechanisms of L. monocytogenes involved in nisin resistance have not yet to be fully defined. A mariner transposon library was constructed in L. monocytogenes, leading to the identification of 99 genes associated with the innate resistance to nisin via Transposon sequencing (Tn-seq) analysis. To validate the accuracy of the Tn-seq results, we constructed five mutants (ΔyqgS, ΔlafA, ΔvirR, ΔgtcA, and Δlmo1464) in L. monocytogenes. The results revealed that yqgS and lafA, the lipoteichoic acid-related genes, were essential for resistance to nisin, while the gtcA and lmo1464 mutants showed substantially enhanced nisin resistance. Densely wrinkled, collapsed surface and membrane breakdown were shown on ΔyqgS and ΔlafA mutants under nisin treatment. Deletion of yqgS and lafA altered the surface charge, and decreased the resistance to general stress conditions and cell envelope-acting antimicrobials. Furthermore, YqgS and LafA are required for biofilm formation and cell invasion of L. monocytogenes. Collectively, these results reveal novel mechanisms of nisin resistance in L. monocytogenes and may provide unique targets for the development of food-grade inhibitors for nisin-resistant foodborne pathogens. IMPORTANCE Listeria monocytogenes is an opportunistic Gram-positive pathogen responsible for listeriosis, and is widely present in a variety of foods including ready-to-eat foods, meat, and dairy products. Nisin is the only licensed lantibiotic by the FDA for use as a food-grade inhibitor in over 50 countries. A prior study suggests that L. monocytogenes are more resistant than other Gram-positive pathogens in nisin-mediated bactericidal effects. However, the mechanisms of L. monocytogenes involved in nisin resistance have not yet to be fully defined. Here, we used a mariner transposon library to identify nisin-resistance-related genes on a genome-wide scale via transposon sequencing. We found, for the first time, that YqgS and LafA (Lipoteichoic acid-related proteins) are required for resistance to nisin. Subsequently, we investigated the roles of YqgS and LafA in L. monocytogenes stress resistance, antimicrobial resistance, biofilm formation, and virulence in mammalian cells.


Assuntos
Proteínas de Bactérias/metabolismo , Lipopolissacarídeos/metabolismo , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/metabolismo , Nisina/farmacologia , Ácidos Teicoicos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes , Doenças Transmitidas por Alimentos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Listeria monocytogenes/genética , Listeriose , Virulência/efeitos dos fármacos
20.
J Immunol ; 208(5): 1155-1169, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35110421

RESUMO

CD8+ T cells are critical for the immune response to pathogens and tumors, and CD8+ T cell memory protects against repeat infections. In this study, we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of CD8+ T cell immune responses. Mice with a T cell-specific deletion of ATF7ip have a CD8+ T cell-intrinsic enhancement of Il7r expression and Il2 expression leading to enhanced effector and memory responses. Chromatin immunoprecipitation sequencing studies identified ATF7ip as a repressor of Il7r and Il2 gene expression through the deposition of the repressive histone mark H3K9me3 at the Il7r gene and Il2-Il21 intergenic region. Interestingly, ATF7ip targeted transposable elements for H3K9me3 deposition at both the IL7r locus and the Il2-Il21 intergenic region, indicating that ATF7ip silencing of transposable elements is important for regulating CD8+ T cell function. These results demonstrate a new epigenetic pathway by which IL-7R and IL-2 production are constrained in CD8+ T cells, and this may open up new avenues for modulating their production.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Interleucina-2/biossíntese , Receptores de Interleucina-7/biossíntese , Proteínas Repressoras/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Imunoprecipitação da Cromatina , Elementos de DNA Transponíveis/genética , Deleção de Genes , Inativação Gênica , Histonas/genética , Humanos , Interleucina-2/metabolismo , Listeria monocytogenes/imunologia , Listeriose/imunologia , Listeriose/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/metabolismo , Proteínas Repressoras/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...