Listeria Monocytogenes Infection Research Articles

First Molecular Identification and Whole Genome Sequencing of Listeria monocytogenes Isolated From an African Lion.

Listeria monocytogenes (LM) is a zoonotic pathogen that causes sporadic infectious listeriosis, which is a foodborne disease associated with consumption of contaminated food or feed. The internal organs of an African lion from a zoo in Shanghai were analysed to determine the cause of death. LM infection was suspected on the basis of the clinical symptoms and pathological changes and confirmed by polymerase chain reaction, whole genome sequencing and phylogenetic analysis. This is the first report of LM infection of an African lion in China.

Source attribution of Listeria monocytogenes in the Netherlands

The aim of this study was to determine the relative contributions of various potential food sources of human listeriosis and to identify source-specific risk factors, at exposure level, for human Listeria monocytogenes (Lm) infection. To achieve this, available Lm isolates from human cases (n = 756) and food/animal sources (n = 950) from national surveillance systems in the Netherlands (2010−2020) were whole genome sequenced. Additionally, questionnaire-based exposure data for human cases was collected. Source attribution analysis was performed using a Random Forest model based on core-genome multilocus sequence typing (cgMLST). Risk factors for human Lm infection of cattle, chicken and seafood origin were determined using beta regression analysis on the cgMLST-based attribution estimates. Results indicated that the 756 human Lm isolates were mainly attributed to cattle (62.3 %), chicken (19.4 %), and seafood (16.9 %). Specifically, fresh meat (86.2 %), including fresh bovine meat (43.7 %) and fresh chicken meat (39.3 %), accounted for most cases. These attributions stemmed from Lm contamination of either the food products or their production environments. Consumption of steak tartare and smoked salmon was associated with an increased risk of human Lm infections attributed to cattle and seafood, respectively, while no specific risk factors for chicken-borne listeriosis were identified. This study indicated that Lm isolates of cattle origin, particularly those from fresh bovine meat and associated production environments, are estimated to be the primary cause of human listeriosis in the Netherlands. This aligns with several other European source attribution studies on Lm. Moreover, the identified risk factors for human Lm infection from cattle (i.e. steak tartare) and seafood (i.e. smoked salmon) clearly indicated their attributable sources. This joint analysis of core genome and epidemiological data provided novel insights into the origins and transmission pathways of human listeriosis.

The divergent outcome of IL-4Rα signalling on Foxp3 T regulatory cells in listeriosis and tuberculosis.

Forkhead box P3 (Foxp3) T regulatory cells are critical for maintaining self-tolerance, immune homeostasis, and regulating the immune system. We investigated interleukin-4 receptor alpha (IL-4Rα) signalling on T regulatory cells (Tregs) during Listeria monocytogenes (L. monocytogenes) infection using a mouse model on a BALB/c background, specifically with IL-4Rα knockdown in Tregs (Foxp3creIL-4Rα-/lox). We showed an impairment of Treg responses, along with a decreased bacterial burden and diminished tissue pathology in the liver and spleen, which translated into better survival. Mechanistically, we observed an enhancement of the Th1 signature, characterised by increased expression of the T-bet transcription factor and a greater number of effector T cells producing IFN-γ, IL-2 following ex-vivo stimulation with heat-killed L. monocytogenes in Foxp3creIL-4Rα-/lox mice. Furthermore, CD8 T cells from Foxp3creIL-4Rα-/lox mice displayed increased cytotoxicity (Granzyme-B) with higher proliferation capacity (Ki-67), better survival (Bcl-2) with concomitant reduced apoptosis (activated caspase 3). In contrast to L. monocytogenes, Foxp3creIL-4Rα-/lox mice displayed similar bacterial burdens, lung pathology and survival during Mycobacterium tuberculosis (M. tuberculosis) infection, despite increased T cell numbers and IFN-γ, TNF and IL-17 production. Our results demonstrated that the diminished IL-4Rα signalling on Foxp3+ T regulatory cells resulted in a loss of their functionality, leading to survival benefits in listeriosis but not in tuberculosis.

Lysteria Monocytogenes Infection during Monochorionic Twin Pregnancy: Case Report and Review of the Literature.

Listeriosis is a rare but severe foodborne disease caused by Listeria Monocytogenes (LM), a small facultative intracellular bacillus. When occurring in pregnant women, it can be vertically transmitted to the fetus and the newborn. Infected women usually display aspecific and mild symptoms, and rarely develop the severe forms of the disease (such as neurolisteriosis). On the contrary, fetal and neonatal listeriosis can lead to complications such as fetal loss, preterm birth, neonatal sepsis, and respiratory distress syndrome (RDS). Prompt diagnosis is one of the main challenges because of the aspecific presentation of the disease; therapy relies on antibiotics that reach high intracellular concentration and can penetrate and pass the placenta reaching the fetus. Herein we report an infrequent case of LM infection involving a woman with monochorionic diamniotic twin pregnancy, followed by a comprehensive review of the available literature on listeriosis in pregnancy.

Clinical and microbiological characteristics and follow-up of invasive Listeria monocytogenes infection among hospitalized patients: real-world experience of 16 years from Hungary

PurposeInvasive Listeria monocytogenes infection is rare, but can lead to life-threatening complications among high-risk patients. Our aim was to assess characteristics and follow-up of adults hospitalized with invasive L. monocytogenes infection.MethodsA retrospective observational cohort study was conducted at a national referral center between 2004 and 2019. Patients with proven invasive listeriosis, defined by the European Centre for Disease Prevention and Control criteria, were included. Data collection and follow-up were performed using the hospital electronic system, up until the last documented visit. The primary outcome was in-hospital all-cause mortality, secondary outcomes included residual neurological symptoms, brain abscess occurrence, and requirement for intensive care unit (ICU) admission.ResultsAltogether, 63 cases were identified (57.1% male, median age 58.8 ± 21.7 years), and 28/63 developed a complicated disease course (44.4%). At diagnosis, 38/63 (60.3%) presented with sepsis, 54/63 (85.7%) had central nervous system involvement, while 9/63 (14.3%) presented with isolated bacteremia. Frequent clinical symptoms included fever (53/63, 84.1%), altered mental state (49/63, 77.8%), with immunocompromised conditions apparent in 56/63 (88.9%). L. monocytogenes was isolated from blood (37/54, 68.5%) and cerebrospinal fluid (48/55, 87.3%), showing in vitro full susceptibility to ampicillin and meropenem (100% each), gentamicin (86.0%) and trimethoprim/sulfamethoxazole (97.7%). In-hospital all-cause mortality was 17/63 (27.0%), and ICU admission was required in 28/63 (44.4%). At discharge, residual neurological deficits (11/46, 23.9%) and brain abscess formation (6/46, 13.0%) were common.ConclusionAmong hospitalized adult patients with comorbidities, invasive L. monocytogenes infections are associated with high mortality and neurological complications during follow-up.

A 48-year-old man with fever, nauseous, vomiting, and dizzy: A CARE case report.

Listeria monocytogenes (LM) is an important foodborne bacterium, and LM meningoencephalitis is rare in clinical practice, with poor prognosis in severe patients. It is prone to misdiagnosis in clinical practice. We first reported a case of severe LM meningoencephalitis with muscle lesions and evaluated the comprehensive condition. A 48-year-old man had a fever and was admitted to the neurology department due to dizziness, nausea, and vomiting for 20 days. LM meningoencephalitis complicated with muscle lesions. We used moxifloxacin 0.4 g, qd, meropenem 2 g, q8h, and dexamethasone 10 mg, qd to reduce exudation and adhesion. Then due to consideration of side effects, we increased the dose of ampicillin by 2 g, q4h, stopped using meropenem and moxifloxacin, and turned to maintenance treatment with dexamethasone and ampicillin. We comprehensively managed his vital signs and physical organ functions, we also controlled some comorbidities. During the hospitalization period thereafter, we used intravenous anti-infection treatment with moxifloxacin 0.4 g, qd, ampicillin 0.5 g, q4h. Half a year later, the reexamination showed only protein elevation in cerebrospinal fluid and hydrocephalus in MRI. Afterward, the symptoms did not recur again. The patient recovered well after discharge. LM meningoencephalitis complicated with lower limb muscle lesions is clinically rare. This report focuses on relevant treatment plans, which provide value for the examination and comprehensive management of patients with LM infection in the future.

The chaperone PrsA2 regulates the secretion, stability, and folding of listeriolysin O during Listeria monocytogenes infection.

Lm is a ubiquitous food-borne pathogen that can cause severe disease to vulnerable populations. During infection, Lm relies on a wide repertoire of secreted virulence factors including the LLO that enables the bacterium to invade the host and spread from cell to cell. After membrane translocation, secreted factors must become active in the challenging bacterial cell membrane-wall interface. However, the mechanisms required for secreted protein folding and function are largely unknown. Lm encodes a chaperone, PrsA2, that is critical for the activity of secreted factors. Here, we show that PrsA2 directly associates and protects the major Lm virulence factor, LLO, under conditions corresponding to the host cytosol, where LLO undergoes irreversible denaturation. Additionally, we identify molecular features of PrsA2 that enable its interaction with LLO. Together, our results suggest that Lm and perhaps other Gram-positive bacteria utilize secreted chaperones to regulate the activity of pore-forming toxins during infection.

Listeriosis in Poland in 2012-2021.

The aim of the study is to present and evaluate the epidemiological situation of listeriosis in Poland in the years 2012-2021. The analysis material consisted of data from individual epidemiological case reports on listeriosis submitted to the Department of Epidemiology of Infectious Diseases and Surveillance of the NIPH NIH - NRI by state sanitaryepidemiological stations in the form of paper questionnaires (2012-2019) and in the electronic form through the EpiBaza system (2020 and 2021), as well as aggregated data from the bulletin "Infectious Diseases and Poisoning in Poland". Between 2012 and 2021, a total of 896 cases of listeriosis were registred in Poland. The median incidence was 0.23 per 100,000 population, which was an increase by 52.2% compared to the previous 5-year period (2007-2011). Every year, more than 90% of cases were hospitalized. The highest percentage of patients were in the age group >60 years old (65.5%). From 2012 to 2019 (in the years when information on cases was collected on a paper form), a total of 275 deaths of patients from listeriosis were recorded (38.4% of all reported cases). According to data from the EpiBaza system, in 2020 and 2021 there were 5 (8.33%) and 25 (20.83%) deaths due to listeriosis. A total of 92.1% of patients with listeriosis had significant predisposing factors for the occurrence of this disease, most of which were associated with neoplasia and heart disease and were present in half of all cases. As part of routine surveillance, no epidemic outbreak associated with Listeria monocytogenes infection was reported in Poland in the years 2012-2021.A total number of 49 pregnant women with listeriosis were reported during described period. Between 2012 and 2021, 37 cases of congenital listeriosis were reported. The median of incidence was 1.07/100 thousand live births, a decrease of 26% compared to the previous 5-year period (2007-2011). Of all congenital infections in newborns, 12 deaths (32.43%) were reported. The epidemiology of listeriosis is changing both in the EU/EEA countries and in Poland: the incidence is increasing and the distribution of cases in different age groups is changing, affecting primarily the elderly, especially those with predisposing diseases. Although 2020 tere was a decrease in the number of cases at EU level, possibly related to the COVID-19 pandemic, the overall trend of listeriosis cases isincreasing. The clinical condition has a significant impact on the course of L. monocytogenes infection: in healthy people, infection is usually asymptomatic. The disease primarily affects immunocompromised people. In contrast, infection of pregnant women can lead to premature birth, miscarriage, meningitis and neonatal sepsis with mortality rate of 20-30%. The growing trend in listeriosis is alarming and requires greater attention in terms of prevention and control of the disease.

Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes Infection: A 12-Year Hospital-Based Study in Xi'an, China.

Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Increased incidence and mortality from Listeria monocytogenes infection in Spain

ObjectivesListeria monocytogenes (LM) is a health threat worldwide given its high mortality and the growing of high-risk susceptible populations. MethodsAll hospitalizations with a diagnosis of LM in the National Registry of Hospital Discharges were examined in Spain from 2000 to 2021. ResultsA total of 8152 hospital admissions with LM were identified. The mean age was 59.5 years and 48% were immunosuppressed (IS).The rate of LM hospitalizations increased from 5 per 1 million population in 2000 to 8.9 in 2021 (p < 0.001). A foodborne outbreak in Andalusia determined a sharp increase in admissions with LM during 2019. The COVID-19 pandemic and lockdowns were associated with a decrease in LM admissions.The overall in-hospital mortality was 16.7%. The number of deaths in patients hospitalized with LM rose from 7.8 per 100,000 deceased in 2000 to 18 in 2021 (p < 0.001). After adjustment, age >65 years (odds ratio [OR] = 2.16), sepsis (OR = 2.60), meningoencephalitis (OR = 1.72), endocarditis (OR = 2.0), neonatal listeriosis (OR = 2.10) and IS (OR = 2.09) were associated with mortality. ConclusionsThe number of patients hospitalized with LM in Spain has increased significantly from 2000 to 2021. The increase in the rate of admissions and deaths was largely driven by the growing proportion of elderly and IS patients.

Regulation and activity of Runx2 in CD8+ T cells responding to infection promotes long-term survival

Abstract Constitutive expression of Runx family proteins in CD8 T cells and maintenance of accessibility surrounding Runx motifs in regulatory regions of lineage-specific loci suggest that they may play a role in establishing and maintaining the epigenetic state of CD8 T cells. Additionally, Runx proteins possess a highly homologous DNA binding domain, leading not only to redundancies, but also potential competition between Runx proteins for the same genomic binding sites. While Runx1 and Runx3 have well known roles in the development of CD8 T cells, the function of Runx2 is not well established. To further explore the function of Runx2, our lab utilizes a model of retroviral overexpression and CRISPR knockout of Runx proteins in OT-1 CD8 T cells. Adoptive transfer of Runx2 overexpressing or knockout cells followed by ovalbumin-expressing Listeria monocytogenes (LmOva) infection suggests that Runx2 activity is important for the expression and maintenance of genes needed for long-term survival and function, such as Tcf7 and Il7ra. Data analyzed from the literature and chromatin analyses from our lab suggest that Runx proteins may compete for binding sites and drive opposing transcriptional and epigenetic profiles in CD8 T cells after infection. Preliminary data also give insight into the mechanisms controlling Runx2 expression, suggesting that the signals received during priming may affect the balance of Runx protein activity.

Enhanced host protection and survival to Listeria monocytogenes infection after small molecule innate training

Abstract Homeostatic training of innate immunity can improve protection against later infections. Our lab recently reported on small molecules that induce trained immunity in vitro. Here, we aim to show the protective potential of flunisolide (FN) using live infection model. We hypothesized FN training will alter hematopoiesis and innate functionality to improve outcome to L. monocytogenes. At homeostasis, FN training skewed towards GMP and MEP lineages and away from CLP lineage. To confirm FN-induced protection, mice were infected i.n. At d3 post-infection, FN mice showed lower pathogen burden in spleen, blood, and lung. Notably, systemic burden was lower in FN mice at d2 and d3. This may be due to improved immune functionality that led to faster clearance. To test this, phagocytosis and ROS levels at d3 were measured but no significant changes were seen. Further studies on lung immune functionality and earlier timepoints may show what hinders pathogen dissemination. BM at d7 after infection showed higher percentage of Lin+ in control and Lin- cells in FN mice. This suggests BM was recovering to homeostasis in FN mice, while inflammation control was active in control. Also, BM of FN mice had significantly higher percentage of CLP, suggesting earlier onset of adaptive immune response. Furthermore, FN mice showed improved survival up to d7. We showed FN can induce innate training, altering BM landscape at homeostasis and after infection, with improved response to L. monocytogenes.

Intestinal linoleic acid contributes to the protective effects of Akkermansia muciniphila against Listeria monocytogenes infection in mice.

Akkermansia muciniphila pretreatment mitigated Listeria monocytogenes infection in mice. A. muciniphila improved gut microbiota disturbed by L. monocytogenes infection and significantly increased the level of intestinal linoleic acid in mice. Linoleic acid strengthened the intestinal epithelial barrier and reduced pathogen translocation partly by regulating NF-κB/MLCK pathway in a GPR40-dependent manner.

Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients: Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.

Impaired meningeal lymphatic drainage in Listeria monocytogenes infection.

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.

Abstract 2654: HPK1 inhibits CD8+ T cell effector gene expression following T cell activation

Abstract Hematopoietic progenitor kinase 1 (HPK1) has been shown to act as a negative regulator of T cell receptor signaling and of subsequent effector T cell function. Inhibiting HPK1 to enhance T cell activity has emerged as a promising strategy for cancer immunotherapy. Upon T cell receptor engagement, the kinase domain of HPK1 is activated and targets components of the T cell receptor (TCR) signaling pathway for degradation, including SLP76. However, the molecular events connecting HPK1 kinase activity to observed T cell functions downstream of proximal TCR signaling are not well understood. Through transcriptional profiling of HPK1-kinase-dead (HPK1-KD) versus wild-type CD8+ T cells following an acute, attenuated Listeria monocytogenes infection, we observed increased expression of many genes associated with T cell activation and effector function, including changes in expression of several key transcription factors and their targets. Upon activation, HPK1-KD T cells, as well as T cells treated with our small-molecule HPK1 inhibitor, produce higher levels of a wide range of effector cytokines in vitro and in vivo. Treatment of mice with the HPK1 inhibitor also inhibited tumor growth in several syngeneic tumor models. These data expand our understanding of the role of HPK1 in inhibiting CD8+ T cell effector programs, and, importantly, the impact of HPK1 inhibitors on T cell function. Citation Format: Rachel Y. Ames, Rongqi Zhao, Parker Mace, Adam Grant, Guorui Xie, Heather Milestone, Molly Grandcolas, Eva Fang, Nicolae Kiosea, Stephen Wong, Martin Brovarney, Scott Jacobson, Danilo Nebalasca, Jorge Arguello, Blanca Gomez, Hiranmayee Kandala, Michelle Y. Ko, Lan Nguyen, Omar Robles, Grant Shibuya, Anton A. Shakhmin, Parcharee Tivitmahaisoon, Vi-Anh Vu, Ashkaan Younai, Mikhail Zibinsky, Babu Subramanyam, Daniel Poon, Mohsen Sabouri Ghomi, David J. Wustrow, Paul D. Kassner, George E. Katibah, Dirk G. Brockstedt. HPK1 inhibits CD8+ T cell effector gene expression following T cell activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2654.

Rational Design of a Robust G-Quadruplex Aptamer as an Inhibitor to Alleviate Listeria monocytogenes Infection.

Listeria monocytogenes (LM) is one of the most invasive foodborne pathogens that cause listeriosis, making it imperative to explore novel inhibiting strategies for alleviating its infection. The adhesion and invasion of LM within host cells are partly orchestrated by an invasin protein internalin A (InlA), which facilitates bacterial passage by interacting with the host cell E-cadherin (E-Cad). Hence, in this work, we proposed an aptamer blocking strategy by binding to the region on InlA that directly mediated E-Cad receptor engagement, thereby alleviating LM infection. An aptamer GA8 with a robust G-quadruplex (G4) structural feature was designed through truncation and base mutation from the original aptamer A8. The molecular docking and dynamics analysis showed that the InlA/aptamer GA8 binding interface was highly overlapping with the natural InlA/E-Cad binding interface, which confirmed that GA8 can tightly and stably bind InlA and block more distinct epitopes on InlA that involved the interaction with E-Cad. On the cellular level, it was confirmed that GA8 effectively blocked LM adhesion with an inhibition rate of 78%. Overall, the robust G4 aptamer-mediated design provides a new direction for the development of inhibitors against other wide-ranging and emerging pathogens.

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

Memory CD8+ T cell generation is crucial for pathogen elimination and effective vaccination against infection. The cellular and molecular circuitry that underlies the generation of memory CD8+ T cells remains elusive. Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense. Here we report that eosinophils are required for the generation of memory CD8+ T cells by inhibiting CD8+ T cell apoptosis. Eosinophil-deficient mice display significantly impaired memory CD8+ T cell response and weakened resistance against Listeria monocytogenes (L.m.) infection. Mechanistically, eosinophils secrete interleukin-4 (IL-4) to inhibit JNK/Caspase-3 dependent apoptosis of CD8+ T cells upon L.m. infection in vitro. Furthermore, active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+ T cell apoptosis during early stage of L.m. infection in vivo. Adoptive transfer of wild-type (WT) eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+ T cell memory responses. Together, our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+ T cell memory and enhances immune defense against L.m. infection. Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens

Oxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by which the host enables innate immunity activation during oxidative burst remains largely unknown. Here, we demonstrate that S-nitrosoglutathione (GSNO), the main endogenous SNO, attenuates innate immune responses against herpes simplex virus-1 (HSV-1) and Listeria monocytogenes infections. Mechanistically, GSNO induces the S-nitrosylation of stimulator of interferon genes (STING) at Cys257, inhibiting its binding to the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Alcohol dehydrogenase 5 (ADH5), the key enzyme that metabolizes GSNO to decrease cellular SNOs, facilitates STING activation by inhibiting S-nitrosylation. Concordantly, Adh5 deficiency show defective STING-dependent immune responses upon microbial challenge and facilitates viral replication. Thus, cellular oxidative burst-induced RNS attenuates the STING-mediated innate immune responses to microbial infection, while ADH5 licenses STING activation by maintaining cellular SNO homeostasis.

Clinical characteristics and prognosis of pediatric Listeria monocytogenes meningitis based on 10-year data from a large children's hospital in China.

This study aims to summarize the clinical characteristics and prognosis of Listeria monocytogenes (LM) meningitis in children in Chongqing, China. A retrospective analysis of the clinical data and follow-up results of 20 LM meningitis patients admitted to the Children's Hospital of Chongqing Medical University (CHCMU) from January 2012 to December 2022 was performed. The LM meningitis incidence rate was between 0 and 14.3 per 100,000 persons. The median age at onset was 8.98 months. There were five neonate cases, which all had perinatal abnormalities. Seven non-neonatal cases (7/15, 46.7%) had a documented history of contaminated food intake. One case had primary immunodeficiency. The most common symptoms were fever (20/20), altered consciousness (19/20), and vomiting (15/20). Seven cases had seizures, eight cases had cranial nerve involvement, eight cases had positive Babinski sign, and 10 cases had positive meningeal signs. The most common complications were hyponatremia (6/20), hypokalemia (6/20), respiratory failure (5/20), subdural effusion (3/20), and hydrocephalus (2/20). Treatment primarily involved monotherapy or combination therapy with meropenem (15/20) and ampicillin (10/20). Fifteen cases were treated with monotherapy or combination therapy using vancomycin. Twelve cases were successfully followed up from 10 months to 9 years and 6 months, and all had favorable long-term outcomes. LM meningitis incidence in children is low and with nonspecific clinical manifestations. Strengthening food hygiene and safety education, and avoiding infections during pregnancy are important to prevent LM infection in neonates and high-risk individuals. Meropenem and ampicillin are the preferred treatments. Early diagnosis and treatment can improve prognosis.IMPORTANCEThe incidence of LM meningitis is extremely low, and there is currently no standardized treatment. We conducted a retrospective analysis of ten years of data from CHCMU regarding diagnosed LM meningitis cases, aiming to provide clinical evidence for the diagnosis and treatment.