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Aim To review the clinical features of systemic lupus erythematosus (SLE) complicated by central nervous system (CNS) infection due to Listeria monocytogenes. Method A patient with SLE receiving high-dose glucocorticoids combined with cyclophosphamide who developed multiple brain abscesses due to Listeria infection is described. The case is compared with known cases in a literature review. Results A review of the literature showed that CNS infections are rare bacterial complications of SLE, but they can be a significant cause of mortality, especially those due to L. monocytogenes. The most significant risk factor for listerial meningitis is a prior history of receiving immunosuppressive therapy. At-risk patients should avoid unpasteurized milk and soft cheeses along with deli-style, ready-to-eat prepared meats, particularly poultry products. The case we report is the fifth SLE patient with multiple brain abscesses due to L. monocytogenes, and the first to be discharged with no sequelae. Timely and accurate identification and treatment of CNS infections and neuropsychiatric lupus are very important for favorable disease prognosis. Conclusion Repeated blood culture is helpful for early diagnosis, and empirical anti-infective treatment that covers L. monocytogenes is recommended for SLE patients with risk factors when CNS infection occurs. A comprehensive assessment might be helpful to distinguish CNS infections from neuropsychiatric SLE. For severe infection, the dosage of steroids does not need to be reduced immediately but can be gradually adjusted based on the results of a comprehensive evaluation of the disease.

Localized Listeria infection predominantly occurs in the prosthetic and hip joints. We herein report a case of Listeria monocytogenes ankle osteomyelitis in a 73-year-old man receiving adalimumab who was transferred to our hospital because of suspected rheumatoid arthritis (RA) flare. He reported a four-month history of left ankle swelling. A surgical biopsy revealed L. monocytogenes osteomyelitis in the left tibia and talus bones. The patient was successfully treated with antibiotics and surgical debridement. Thus, infection due to L. monocytogenes can present as ankle osteomyelitis in immunocompromised patients and may mimic an RA flare.

ObjectivesTo describe the epidemiology, age at infection, clinical characteristics and outcome of listeria infection in young infants to inform management and empiric antibiotic choice in young infants.DesignProspective 2-year surveillance of Listeria monocytogenes infection in young infants detected through the British Paediatric Surveillance Unit ‘orange card’ system and triangulated with the public health laboratories.SettingNational population study (England, Wales, Scotland and the Ireland)PatientsAll infants under 90 days with proven or probable invasive listeriosisMain outcome measuresIncidence, mortality, age of infection, clinical characteristics and outcomeResultsDuring a 2-year period (2017–2019), 27 cases of listeriosis in infants ConclusionsInvasive listeriosis in young infants in the UK and Ireland is rare and presents early in the neonatal period. National guidelines that recommend the use of amoxicillin as part of empiric regimes for sepsis and meningitis in infants over 1 month of age should be modified.

Introduction . Listeriosis is a foodborne infection, especially dangerous for people in at-risk groups. Susceptibility to listeria infection is determined by a complex of reasons: environmental factors, host immune status, and pathogen virulence. The susceptibility to listeriosis can also be aggravated by previous infections, especially viral infections, which demonstrate a steadily increasing number of identified pathogens. The aim of our study was to present molecular and genetic characterization of pathogens causing sporadic invasive listeriosis in a megalopolis, primarily during the peak of influenza and ARVI incidence. Materials and methods . Listeria monocytogenes isolates were collected from 18 hospitalized patients at hospitals in Moscow, from November 2018 to October 2019. The first comparison group was represented by isolates from food products and fish preserves. The second comparison group included previously examined environmental isolates. The clinical isolates were examined by using multilocus sequence typing techniques, including the standard MLST scheme extended by loci of internalin genes. Isolates of the autochthonous genotype (ST7) were compared through whole-genome sequencing and subsequent analysis of the core genome (cgMLST). Results . In cases of invasive listeriosis, 44% of isolates were isolated from patients with listeriosis; 27% of isolates were obtained from patients with meningitis. L. monocytogenes of phylogenetic lineage II prevailed in these groups of cases that occurred when the epidemic threshold for influenza was crossed during the 2018/2019 season. Listeria pneumonia identified in the senior age group occurred during the season of autumn ARVI and was primarily caused by L. monocytogenes of phylogenetic lineage I. The examination of genomes of ST7 isolates demonstrated identity between the core genomes of bacteria isolated from the mother-infant pair. Out of ST7 food isolates most closely related to the clinical ones was the isolate from meat (23 locus differences, the common deletion in the MFS transporter locus). Analyzing invasive listeriosis, the comparison between the list of the identified genotypes and the data from European countries showed that each country had its own specific range of genotypes, though ST7 was detected in all the examined samples. Conclusions . Along with the monitoring of food manufacturing and storage, timely vaccination against seasonal respiratory infections and use of personal protective equipment in public spaces can reduce the risk of listeriosis incidence in at-risk groups.

As a specialized subset of intestinal epithelial cells (IECs), goblet cells (GCs) play an important role during the antibacterial response via mucin production. However, the regulatory mechanisms involved in GC differentiation and function during infection, particularly the role of immune cell–IEC cross-talk, remain largely unknown. In this study, using Villin∆Ltbr conditional knockout mice, we demonstrate that LTβR, expressed on IECs, is required for GC hyperplasia and mucin 2 (MUC2) expression during Listeria infection for host defense but not homeostatic maintenance in the naive state. Analysis of single gene-deficient mice revealed that the ligand lymphotoxin (LT), but not LIGHT, and type 3 innate lymphoid cells (ILC3s), but not conventional T cells, are required for MUC2-dependent Listeria control. Conditional deficiency of LT in ILC3s further confirmed the importance of LT signals derived from ILC3s. Lack of ILC3-derived LT or IEC-derived LTβR resulted in the defective expression of genes related to GC differentiation but was not correlated with IEC proliferation and cell death, which were found to be normal by Ki-67 and Annexin V staining. In addition, the alternative NF-κB signaling pathway (involving RelB) in IECs was found to be required for the expression of GC differentiation-related genes and Muc2 and required for the anti-Listeria response. Therefore, our data together suggest a previously unrecognized ILC3–IEC interaction and LT–LTβR–RelB signaling axis governing GC differentiation and function during Listeria infection for host defense.

Background Pericarditis is a common cardiology presentation, most often due to a viral or idiopathic cause. Listeria as a cause of pericarditis is rare. Listeria is an infection that is readily treatable with antibiotics following accurate identification. Without adequate treatment, Listeria infection has a high mortality rate. Case summary In this case, a fit and well 59-year-old man complained of headaches and fever to the emergency department (ED). He was provisionally diagnosed with giant cell arteritis (GCA) and commenced on management pathways for GCA. He represented to the ED with chest pain and electrocardiogram (ECG) changes suggestive of a clinical presentation of pericarditis. He received treatment for idiopathic pericarditis with no clinical resolution. Cardiac magnetic resonance imaging (MRI) showed myopericardial inflammation associated with a right atrial mural thrombus. After 2 weeks of poor treatment response, peripheral blood cultures grew Listeria monocytogenes and the patient responded well to antibiotic treatment. Repeat cardiac MRI after an extended course of antibiotics showed resolution of MRI signs. Discussion This is a case of Listeria myopericarditis. Physicians should consider rarer causes of myopericarditis in treatment resistance cases. Cardiac MRI has utility in atypical or treatment resistant patients to assess myopericardial inflammation and response to treatment.

Infectious diseases such as Listeria monocytogenes infection pose a great threat to the health of human beings and the development of livestock and poultry farming. Currently the treatment of Listeria infection mainly relies on antibiotics, which may result in excessive antibiotic residues in livestock and poultry products, as well as causing an increase in the occurrence of zoonotic diseases. Here, we demonstrate that Succinoglycan Riclin promoted the clearance of Listeria in the in vitro and in vivo infection model. The expression and secretion of inflammatory cytokines including IL-6 and IL-1β were significantly increased after Riclin treatment upon infection. The protective effect of Riclin was mainly through activating MAPK/IL-6 axis. HO-1/IL-1β signaling pathway was less important in this process. Moreover, Riclin caused significant metabolic changes including pathways involved in glycolysis, protein synthesis and oxidative stress during Listeria infection. These results suggest a potential use of Succinoglycan Riclin as non-antibiotic preventive and therapeutic anti-microbial agent in livestock and poultry farming and human diseases.

Listeria monocytogenes, a human foodborne pathogen that causes listeriosis with high-rate mortality, has been reported to be resistant to commonly used antibiotics. New antibiotics or cocktails of existing antibiotics with synergistic compounds are in high demand for treating this multi-drug-resistant pathogen. Fosfomycin is one of the novel and promising therapeutic antibiotics for the treatment of listeriosis. However, some L. monocytogenes strains with the FosX gene were recently reported to survive from the fosfomycin treatment. This work aims to identify FosX inhibitors that can revive fosfomycin in treating resistant L. monocytogenes. Since structures and activities of the FosX protein in L. monocytogenes have been well studied, we used an integrated computational and experimental approach to identify FosX inhibitors that show synergistic effect with fosfomycin in treating resistant L. monocytogenes. Specifically, automated ligand docking was implemented to perform virtual screening of the Indofine natural-product database and FDA-approved drugs to identify potential inhibitors. An in vitro bacterial growth inhibition test was then utilized to verify the effectiveness of identified compounds combined with fosfomycin in inhibiting the resistant L. monocytogenes strains. Two phenolic acids, i.e., caffeic acid and chlorogenic acid, were predicted as high-affinity FosX inhibitors from the ligand-docking platform. Experiments with these compounds indicated that the cocktail of either caffeic acid (1.5 mg/mL) or chlorogenic acid (3 mg/mL) with fosfomycin (50 mg/L) was able to significantly inhibit the growth of the pathogen. The finding of this work implies that the combination of fosfomycin with either caffeic acid or chlorogenic acid is of potential to be used in the clinical treatment of Listeria infections.

Listeria monocytogenes is a gram positive bacterium of public health concern with low morbidity but high mortality rate. Listeriosis in human is usually caused by the consumption of infected animal and food. It is noteworthy that an infected animal such as rat could be potential carrier and vector. Therefore, this study examined the clinic pathological changes associated with Listeria monocytogenes infection in rat. Six (6) Winstar laboratory rats divided into 2 groups. Group 1 was challenged with 0.1-mL saline water as control while the second group was challenged intraperitoneally with 0.1 mL molecularly characterised Listeria monocytogenes (1 × 104 CFU/mL) isolates. The rats were observed for clinical signs and mortality. Haematology, serum and enzymes indices were examined using standard procedures. Then, the liver and kidney of the rats from the two groups were aseptically examined for histopathological changes. The result shows that 33.3% of the rats challenged with Listeria monocytogenes died within 24 h (1 day) while 100% mortality were recorded within 48 h (2 days). There were significant decreases (P

Microbial interaction with the host through sensing receptors, including SIGNR1, sustains intestinal homeostasis against pathogenic inflammation. The newly discovered commensal Propionibacterium strain, P. UF1, regulates the intestinal immunity against pathogen challenge. However, the molecular events driving intestinal phagocytic cell response, including colonic dendritic cells (DCs), by this bacterium are still elusive. Here, we demonstrate that the glycosylation of bacterial large surface layer protein A (LspA) by protein O-mannosyltransferase 1 (Pmt1) regulates the interaction with SIGNR1, resulting in the control of DC transcriptomic and metabolomic machineries. Programmed DCs promote protective T cell response to intestinal Listeria infection and resist chemically induced colitis in mice. Thus, our findings may highlight a novel molecular mechanism by which commensal surface glycosylation interacting with SIGNR1 directs the intestinal homeostasis to potentially protect the host against proinflammatory signals inducing colonic tissue damage.

Background: Listeriosis affects immunosuppressed individual’s especially pregnant women. Maternal infections are usually mild for the woman, but may have devastating effects on the unborn child, including miscarriage, stillbirth, preterm labour and serious neonatal illness. WHO recommends that pregnant women should be educated to avoid foods with high risk of contamination. This study seeks to evaluate knowledge and practices predisposing to listeria infections during pregnancy. Methodology: This is a cross-sectional study on pregnant women, attending the antenatal clinic of Lagos University Teaching Hospital (LUTH) using semi structured questionnaires. The knowledge score of participants was collated and analyzed using SPSS version 26. Results: The mean age of the participants was 32.07 ± 5.6 years. Forty-three (30.7%) women have had previous miscarriages with the mean no of miscarriage of 1.54. Out of 147 participants, only 20 (13.6%) admitted having heard of listeriosis while 127 (86.4%) had never heard of listeriosis and none of the participants has ever been tested for listeriosis. The Overall knowledge score was poor, and this was irrespective of age and duration of pregnancy. However, women with graduate and/or postgraduate degrees were more likely to have heard of Listeriosis (X2 = 10.88, P = 0.028). Conclusion: Our study shows a low level of knowledge about this food-borne illness, which can lead to severe illnesses in pregnant women and their unborn child. It is necessarily to educate pregnant women on the risk of listeriosis. This would be a key factor in creating and implementing accurate measures of prevention and control.

Listeria monocytogenes is a food pathogen responsible for many foodborne disease outbreaks. Listeria innocua is similar to L. monocytogenes, could be considered biologically similar to L. monocytogenes and could be used to predict its behavior. The aims of this work were to isolate Listeria spp. in dairy processing plants, perform genotypic characterization of virulence, evaluate the antimicrobial resistance profile, and verify the sensitivity of the strains to essential oils. Sampling was held in six dairy processing plants in the region of Campinas, Brazil. Seventeen Listeria innocua strains were isolated, all negative for virulence genes inlA, inlB, inlC, inlJ, actA, plcA, and plcB. The strains were resistant to kanamycin (5.9%), penicillin (11.8%), ampicillin (11.8%), cefoxitin (58.8%), clindamycin (76.50%) and oxacillin (100%). The susceptibility of the strains to commercial essential oils (Rosemarinus officinalis, Cymbopogon citratus, Eucalyptus citirodora, Mentha piperita, Piper nigrum, Vetiveria zizanioides, Cymbopogon nardus, Cymbopogon martinii and Pogostemon cablin) was evaluated by Minimum Inhibitory Concentration (MIC) test. The results showed Cymbopogon citratus, Cymbopogon martini, Cymbopogon nardus and Mentha piperita oils were most efficient. The resistance of Listeria innocua isolated in dairy processing plants is worrisome, and the use of essential oils could be an alternative for development of new drugs and products.

The human Listeriosis infection is a food-borne disease caused by the consumption of food products contaminated by the bacterial pathogen, Listeria. In this paper, we propose a mathematical model to analyse the impact of media awareness campaigns on the spread and control of Listeriosis. The model equilibria are determined and the model has three equilibria namely; the disease-free, the Listeria-free, and the endemic equilibria. The food contamination constant (ℛf) is determined and the stability analysis shows that the disease-free steady state is locally asymptotically stable if ℛf 1. Sensitivity analysis is done to determine the model parameters that most affect the severity of the disease. Numerical simulations are carried out to determine the role of media awareness campaigns on the spread of the Listeriosis. The results show that an increase in the intensity of the media awareness campaigns and removal of contaminated food products, a decrease in the contact rate, results in fewer humans getting infected leading to disease eradication, while an increase in the depletion of media awareness campaigns results in more humans been infected with Listeriosis. These findings may significantly impact policy and decision making in the control of Listeriosis disease.

Listeria monocytogenescauses severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that during long-term infection of hepatocytes, a subpopulation ofListeriamay escape eradication by entering a persistence phase in intracellular vacuoles. Here, we examine whether this long-term infection alters hepatocyte defense pathways, which may be instrumental for bacterial persistence. We first optimized cell models of persistent infection in human hepatocyte cell lines HepG2 and Huh7 and primary mouse hepatocytes (PMH). In these cells,Listeriaefficiently entered the persistence phase after three days of infection, while inducing a potent interferon response, of type I in PMH and type III in HepG2, while Huh7 remained unresponsive. RNA-sequencing analysis identified a common signature of long-termListeriainfection characterized by the overexpression of a set of genes involved in antiviral immunity and the under-expression of many acute phase protein (APP) genes, particularly involved in the complement and coagulation systems. Infection also altered the expression of cholesterol metabolism-associated genes in HepG2 and Huh7 cells. The decrease in APP transcripts was correlated with lower protein abundance in the secretome of infected cells, as shown by proteomics, and also occurred in the presence of APP inducers (IL-6 or IL-1β). Collectively, these results reveal that long-term infection withListeriaprofoundly deregulates the innate immune functions of hepatocytes, which could generate an environment favorable to the establishment of persistent infection.

Mast cells in the brain are associated with increased inflammation during the acute period following exposure to infection; these cells are important for destroying the infectious agents. We investigated the relation between histopathological lesions and mast cells in sheep brains infected with Listeria. Pons and medulla regions from 17 infected and eight normal sheep brains were examined. Microabscesses and perivascular infiltration were assessed for histopathology. Mast cells were identified using toluidine blue and Listeria monocytogenes were investigated immunohistochemically. We found a significant increase in mast cells in infected sheep brains that was related directly to the extent of brain lesions. A strong correlation was found between mast cells and microabscess formation. A correlation between bacteria level and brain lesions also was observed, but not between bacteria level and mast cells. Our findings indicate that mast cells are increased following Listeria infection in sheep in proportion to the severity of brain lesions; the increase may contribute to acute inflammatory reactions and also may destroy bacteria directly.

Gamma delta T-cells are commonly found in response to Listeria monocytogenes infection in mice, whereas this same immunological response has only been reported a few times in vivo in humans. Moreover, gamma delta T-cell response in cerebral spinal fluid samples in conjunction with Listeria meningitis has never been described in medical literature to date. Thus, we describe a 64-year-old male who presented with altered mental status, fever, and neck stiffness. After lumbar puncture revealed elevated glucose, protein, lactate dehydrogenase, and white blood cell count, further cytologic analysis was indicated. The CSF showed a markedly hypercellular sample with a lymphocytic pleocytosis, including some enlarged forms with irregular nuclear contours, and rare macrophage containing intracytoplasmic bacteria. Lymphocyte immunophenotyping was performed via flow cytometric analysis, which ultimately revealed a prominent CD4/CD8 negative T-cell population, suggestive of a gamma delta T-cell population. Thus, an initial suspicion of malignancy was considered but was ruled out due to the absence of mass lesion on imaging and overall features including heterogenous lymphocyte morphology. Shortly after, gram stain and cultures were obtained revealing Listeria monocytogenes. Unfortunately, the patient rapidly succumbed to disease following the diagnosis of Listeria meningitis. Studies suggest that gamma delta T-cells are activated by the protein components of Listeria and thus have been found to be an important mediator of resistance to Listeria infection. Studies have also discovered that the level of activation for these T-cells appears to be tissue specific and dose dependent, with most cases occurring within visceral organs. Hence, we herein present the first case of gamma delta T-cell activation due to Listeria monocytogenes within the cerebral spinal fluid of a human patient.

Interleukin-37 (IL-37) is a newly introduced cytokine to interleukin-1 family. Many studies have demonstrated that IL-37 owns immunosuppressive effects against both innate and acquired immune responses via inhibition of several inflammatory mediators. Thence, IL-37 has anti-inflammatory action in some diseases including cancer, autoimmune diseases, cardiovascular diseases and infectious diseases. Recent investigations have reported the important role of IL-37 in immunity against viral, bacterial and fungal infections as they prevent inappropriate immune activation and suppress the inflammation induced by these infectious agents. Thus, IL-37 could play a crucial role in protecting host tissues from injury during infections by damping excessive inflammatory reactions. However, the precise roles of IL-37 in infectious diseases remain largely unknown. The current review shed light on the pivotal role of IL-37 in infectious diseases such as the human immunodeficiency virus-1 (HIV-1), viral myocarditis, hepatitis C virus (HCV), hepatitis B virus (HBV), tuberculosis, leprosy, pneumococcal pneumonia, listeria infection, aspergillosis, candidiasis and eumycetoma. In conclusion, this review reported that IL-37 has a crucial role in reducing infection-associated inflammation and has a good impact on inflammation-induced pathology. However, tight regulation that achieved balance between effector immune responses that required for pathogen elimination and limited tissue damage that resulted from excessive inflammation should be existed in the potential IL-37 therapy to prevent clinical complications of a disease.

The RIPK3-MLKL pathway protects epithelial cells from Listeria monocytogenes invasion. Sai et al. find that Listeria infection activates MLKL but does not induce its oligomerization or necroptotic cell death. Instead, Listeria-activated MLKL directly targets intracellular bacteria and suppresses their replication., RIPK3, a key mediator of necroptosis, has been implicated in the host defense against viral infection primary in immune cells. However, gene expression analysis revealed that RIPK3 is abundantly expressed not only in immune organs but also in the gastrointestinal tract, particularly in the small intestine. We found that orally inoculated Listeria monocytogenes, a bacterial foodborne pathogen, efficiently spread and caused systemic infection in Ripk3-deficient mice while almost no dissemination was observed in wild-type mice. Listeria infection activated the RIPK3-MLKL pathway in cultured cells, which resulted in suppression of intracellular replication of Listeria. Surprisingly, Listeria infection–induced phosphorylation of MLKL did not result in host cell killing. We found that MLKL directly binds to Listeria and inhibits their replication in the cytosol. Our findings have revealed a novel functional role of the RIPK3-MLKL pathway in nonimmune cell-derived host defense against Listeria invasion, which is mediated through cell death–independent mechanisms.

Inflammasome activation exacerbates infectious disease caused by pathogens such as Listeria monocytogenes, Staphylococcus aureus, and severe acute respiratory syndrome coronavirus 2. Although these pathogens activate host inflammasomes to regulate pathogen expansion, the mechanisms by which pathogen toxins contribute to inflammasome activation remain poorly understood. Here we show that activation of inflammasomes by Listeria infection was promoted by amino acid residue T223 of listeriolysin O (LLO) independently of its pore-forming activity. LLO T223 was critical for phosphorylation of the inflammasome adaptor ASC at amino acid residue Y144 through Lyn-Syk signaling, which was essential for ASC oligomerization. Notably, a Listeria mutant expressing LLO T223A was impaired in inducing ASC phosphorylation and inflammasome activation. Furthermore, the virulence of LLO T223A mutant was markedly attenuated in vivo due to impaired ability to activate the inflammasome. Our results reveal a previously unrecognized function of a pathogen toxin that exacerbates infection by promoting phosphorylation of ASC.

RNF213 is a large, poorly characterized interferon-induced protein. Mutations in RNF213 are associated with predisposition for Moyamoya disease (MMD), a rare cerebrovascular disorder. Recently, RNF213 was found to have broad antimicrobial activity in vitro and in vivo, yet the molecular mechanisms behind this function remain unclear. Using mass spectrometry-based proteomics and validation by real-time PCR we report here that knockdown of RNF213 leads to transcriptional upregulation of MVP and downregulation of CYR61, in line with reported pro- and anti-bacterial activities of these proteins. Knockdown of RNF213 also results in downregulation of DDAH1, which we discover to exert antimicrobial activity against Listeria monocytogenes infection. DDAH1 regulates production of nitric oxide (NO), a molecule with both vascular and antimicrobial effects. We show that NO production is reduced in macrophages from RNF213 KO mice, suggesting that RNF213 controls Listeria infection through regulation of DDAH1 transcription and production of NO. Our findings propose a potential mechanism for the antilisterial activity of RNF213 and highlight NO as a potential link between RNF213-mediated immune responses and the development of MMD.

Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillus probiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-κB and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits., Here, the authors characterize the effects of Lactobacillus casei strains engineered to express pathogenic or non-pathogenic Listeria adhesion protein (LAP) in systemic colonization and protection against lethal Listeria monocytogenes infection in mice and show that these engineered strains can colonize the intestine and prevent dissemination of L. monocytogenes and protect against lethal infection while promoting immunomodulatory effects.

Background Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. Case presentation We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. Conclusion To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.

In response to invading pathogens, macrophages metabolically polarize toward Hif1α-induced aerobic glycolysis, requiring increased supply of nutrients. Here, we show that in order to obtain sufficient resources, Drosophila macrophages release the insulin/IGF antagonist ImpL2 in a Hif1α-dependent manner as a reflection of adopted polarization. ImpL2 remotely induces Foxo-mediated lipid mobilization and the release of lipoproteins and carbohydrates from adipose tissue to be utilized by the activated immune system. Although these ImpL2 effects are essential in acute streptococcal infection, they become maladaptive during chronic intracellular Listeria infection. The relevance of our model to mammalian immuno-metabolism is documented by the increased expression of the ImpL2 homolog IGFBP7 in human macrophages exposed to Streptococcus. Therefore, we postulate that ImpL2/IGFBP7 induce resource mobilization, which is beneficial during the acute phase of infection but may act as cachectic factors in patients with cancer, sepsis, or obesity.

Background Peritoneal dialysis (PD)-related peritonitis is a rare but serious complication and is associated with increased morbidity and mortality rates. It is most commonly caused by Staphylococcus aureus or Staphylococcus epidermidis, but infection with Listeria monocytogenes may also occur. Recommendations for antibiotic treatment of a Listeria infection are currently based on a small number of case reports and suggest the administration of ampicillin. But unlike vancomycin or gentamicin, for ampicillin the route of application, the dosage, and the duration of treatment have not yet been established. We report a case in which PD-associated peritonitis due to Listeria infection was treated with ampicillin administered intravenously and intraperitoneally, separately and in combination. Case presentation A 72-year-old man with chronic kidney disease stage 5 dialysis (CKDG5D) secondary to hypertension and diabetes was hospitalised in April 2020 because of PD-related peritonitis caused by a Listeria infection. In accordance with the results of resistance tests, the patient was treated with intravenous ampicillin at a dosage of 6 g twice daily. After initial treatment the leukocyte count in the PD effluent had decreased substantially, but it was permanently reduced only with the addition of intraperitoneal ampicillin (4 g daily). Efficient serum concentrations of ampicillin were determined for both routes of administration, intravenous and intraperitoneal. Conclusion This is the first case report demonstrating that PD-related peritonitis due to Listeria monocytogenes infection can be treated with intraperitoneal ampicillin and monitored by the determination of peripheral serum concentrations of ampicillin.

Listeriolysin O (LLO) is a cholesterol-dependent cytolysin that mediates escape of L. monocytogenes from phagosomes and enables the bacteria to grow within the host. LLO is a versatile tool allowing Listeria to trigger several cellular responses. In this study, rapid phosphorylation of ERK1/2 on Caco-2 cells caused by Listeria infection was demonstrated to be highly dependent on LLO activity. The effect could be strongly induced by adding purified recombinant LLO alone and could be inhibited by exogenous cholesterol. Lack of the PEST sequence, known to tightly control cytotoxicity of LLO, did not affect ERK1/2 activation. However, the recombinant non-cytolytic LLOT515AL516A, with mutations in the cholesterol-binding motif, was unable to trigger this response. Recombinant LLON478AV479A, which lacks most of the cytolytic activity, also failed to activate ERK1/2 phosphorylation, and this effect could be rescued when the protein concentration reached a cytolytic level. Infection with an LLO-deficient mutant (Δhly) or the mutant complementing LLOT515AL516A abrogated the capacity of the bacteria to activate ERK1/2. However, infection with the Δhly mutant complementing LLON478AV479A, which retained partial pore-forming ability and could grow intracellularly, was capable of triggering ERK1/2 phosphorylation. Collectively, these data suggest that ERK1/2 activation by L. monocytogenes depends on the permeabilization activity of LLO and more importantly correlates with the cholesterol-binding motif of LLO.

Background Listeria monocytogenes (L. monocytogenes) is a global opportunistic intracellular pathogen that can cause many infections, including meningitis and abortion in humans and animals; thus, L. monocytogenes poses a great threat to public safety and the development of the aquaculture industry. The isolation rate of Listeria monocytogenes in fishery products has always been high. And the pore-forming toxin listeriolysin O (LLO) is one of the most important virulence factors of L. monocytogenes. LLO can promote cytosolic bacterial proliferation and help the pathogen evade attacks from the host immune system. In addition, L. monocytogenes infection can trigger a series of severe inflammatory reactions. Results Here, we further confirmed that morin lacking anti-Listeria activity could inhibit LLO oligomerization. We also found that morin can effectively alleviate the inflammation induced by Listeria in vivo and in vitro and exerted an obvious protective effect on infected cells and mice. Conclusions Morin does not possess anti-Listeria activity, neither does it interfere with secretion of LLO. However, morin inhibits oligomerisation of LLO and morin does reduce the inflammation caused during Listeria infection.

Despite organ shortage, organs from donors with listeria infections have been discarded for transplantation. We present the first-reported case of liver transplantation following listeria encephalitis. The patient was admitted with progressing neurological symptoms after an episode of gastroenteritis. Rhombo-encephalitis was diagnosed, and Listeria monocytogenes was found to be the causative pathogen. Despite proper antibiotic treatment and rapid clearance of bacteremia, he continued to deteriorate and became brain dead, after which organ donation was performed. At procurement, he had been treated with amoxicillin for 9 days. The recipient was treated with pipercillin/tazobactam for 21 days. Besides an anastomotic biliary stricture, necessitating endoscopic dilatation and stenting, further clinical course was uneventful and she is doing well eleven months post-transplant. Our case suggests that listeria encephalitis is not an absolute contra-indication to solid organ donation. We suggest that donors should be treated with adequate antibiotics for at least 48h prior to procurement and advocate confirmation of sterile blood cultures as a prerequisite for donation. According to listeriosis guidelines, we suggest that the recipient should be treated with targeted antibiotics for at least 2 weeks. The risk of transmission should, however, always be balanced carefully against the suspected waiting list mortality.

Background: Congenital CMV infection is the most prevalent congenital infection in the world, and perinatal Listeria infection is an important cause of neonatal sepsis. The identification of these two infections is hard. The PCR technique is a sensitive method, which is not simply available in Iran. Objectives: This study investigated the prevalence of CMV and Listeria in 100 urine samples from under 21-day-old neonates with positive risk factors by PCR electrophoresis and fluorescent end-point detection (FEP) PCR in Tehran referral hospitals. Methods: We used 100 urine samples from neonates admitted to 11 medical centers in Tehran with positive selected clinical symptoms compatible with these infections. Electrophoresis and FEP PCR for CMV and Listeria were performed on all urine samples. For the data analysis, SPSS version 21 software was used, and p values of less than 0.05 were considered significant. Results: We collected 100 urine samples from 100 under 21-day-old neonates, referring to Tehran hospitals. Seven cases were positive for Listeria, and 58 cases were positive for CMV by electrophoresis and FEP PCR. Respiratory distress was the most common clinical finding in both groups. The Mc-Nemar test revealed a statistical agreement between calcification and CMV and meningitis and Listeria (P = 0.18 and 0.07, respectively). There was a positive relationship between the neonates’ age and CMV-positive condition (P = 0.001). This result was not significant among Listeria-positive cases. Conclusions: Screening for CMV and Listeria infections in neonates with clinical features compatible with these intrauterine infections may give important information for their treatment and follow-up.

Summary: CD4+ T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8+ cytotoxic T lymphocyte (CTL) responses, CD4+ T cells can function as helpers (TH) to amplify magnitude and functionality or as regulatory cells (Treg) capable of profound inhibition. It is unclear what determines differentiation to these phenotypes and whether pathogens provoke alternate programs. We find that, depending on the size of initial dose, Listeria infection drives CD4+ T cells to act as TH or induces rapid polyclonal conversion to immunosuppressive Treg. Conversion to Treg depends on the TLR9 and IL-12 pathways elicited by CD8α+ dendritic cell (DC) sensing of danger-associated neutrophil self-DNA. These findings resolve long-standing questions regarding the conditional requirement for TH amongst pathogens and reveal a remarkable degree of plasticity in the function of CD4+ T cells, which can be quickly converted to Treg in vivo by infection-mediated immune modulation. : Dolina et al. show that Listeria infectious dose drives conventional CD4+ T cells to act as TH or mediates conversion to Treg. Differentiation to Treg dominates heightened doses and is promoted by CD8α+ DC TLR9 engagement of neutrophil self-DNA and IL-12 production, revealing plasticity in the function of CD4+ T cells.

During infection, phagocytic cells pursue homeostasis in the host via multiple mechanisms that control microbial invasion. Neutrophils respond to infection by exerting a variety of cellular processes, including chemotaxis, activation, phagocytosis, degranulation and the generation of reactive oxygen species (ROS). Calcium (Ca2+) signaling and the activation of specific Ca2+ channels are required for most antimicrobial effector functions of neutrophils. The transient receptor potential melastatin-2 (TRPM2) cation channel has been proposed to play important roles in modulating Ca2+ mobilization and oxidative stress in neutrophils. In the present study, we use a mouse model of Listeria monocytogenes infection to define the role of TRPM2 in the regulation of neutrophils' functions during infection. We show that the susceptibility of Trpm2−/− mice to L. monocytogenes infection is characterized by increased migration rates of neutrophils and monocytes to the liver and spleen in the first 24 h. During the acute phase of L. monocytogenes infection, Trpm2−/− mice developed septic shock, characterized by increased serum levels of TNF-α, IL-6, and IL-10. Furthermore, in vivo depletion of neutrophils demonstrated a critical role of these immune cells in regulating acute inflammation in Trpm2−/− infected mice. Gene expression and inflammatory cytokine analyses of infected tissues further confirmed the hyperinflammatory profile of Trpm2−/− neutrophils. Finally, the increased inflammatory properties of Trpm2−/− neutrophils correlated with the dysregulated cytoplasmic concentration of Ca2+ and potentiated membrane depolarization, in response to L. monocytogenes. In conclusion, our findings suggest that the TRPM2 channel plays critical functional roles in regulating the inflammatory properties of neutrophils and preventing tissue damage during Listeria infection.

Aminopeptidases that catalyze the removal of N-terminal residues from polypeptides or proteins are crucial for physiological processes. Here, we explore the biological functions of an M29 family aminopeptidase II from Listeria monocytogenes (LmAmpII). We show that LmAmpII contains a conserved catalytic motif (EEHYHD) that is essential for its enzymatic activity and LmAmpII has a substrate preference for arginine and leucine. Studies on biological roles indicate that LmAmpII is required for in vitro growth in a chemically defined medium for optimal growth of L. monocytogenes but is not required for bacterial intracellular infection in epithelial cells and macrophages, as well as cell-to-cell spreading in fibroblasts. Moreover, LmAmpII is found as dispensable for bacterial pathogenicity in mice. Taken together, we conclude that LmAmpII, an M29 family aminopeptidase, can efficiently hydrolyze a wide range of substrates and is required for in vitro bacterial growth, which lays a foundation for in-depth investigations of aminopeptidases as potential targets to defend Listeria infection.

Актуальность проблемы: проблема листериозной инфекции, в настоящее время, актуальна в связи с тем что количество вспышек и людей пострадавших от данной инфекции растёт год от года. А её диагностика затруднительна из - за недостаточного количества дифференциальных признаков. Так же наблюдается достаточно низкая настороженность врачей в связи с низкой заболеваемостью листериозом. Цель исследования: исследование направлено на выявление наиболее значимых диагностических параметров, которые бы позволили осуществлять раннюю диагностику листериоза. Материалы и методы исследования: В данном исследовании были проанализированы два случая листериоза с учётом данных полученных при изучении всех случаев в прошлом. Исследование является обсервационным и относится к типу случай контроль. Статистического анализа данных не было произведено по причине малого объёма выборки. В исследовании использовались данные о диагностических признаках, которые были получены с использованием интеллектуальной системы при обработке массива данных о случаях листериоза. Результаты и их обсуждение и выводы. Среди всех диагностических признаков, как наиболее важные нами были выделены следующие параметры: пол, возраст, иммунный статус, данные эпидемиологического анамнеза, инкубационный период, группа крови, лейкоцитарная формула, свёртывающая система крови, уровень гемоглобина и СОЭ., The problem of Listeria infection is currently relevant due to the fact that the number of outbreaks and people affected by this infection is growing year by year. Its diagnosis is difficult because of the insufficient number of differential signs. There is also a fairly low level of alertness of doctors due to the low incidence of listeriosis. Therefore, the study is aimed at identifying the most significant diagnostic parameters for early diagnosis of listeriosis. In this study, two cases of listeriosis were analyzed, taking into account the obtained data from the study of all cases in the past. The study is observational and belongs to the case control type. There was no statistical analysis of the data due to the small sample size. The study used data on diagnostic signs obtained using an intelligent system when processing an array of data on cases of listeriosis. Among all the diagnostic features, the following parameters were identified as the most important: gender, age, immune status, epidemiological history data, incubation period, blood type, leukocyte formula, blood clotting system, hemoglobin level and ESR.

Listeria monocytogenes causes listeriosis, a potentially fatal food-borne disease. The condition is especially harmful to pregnant women. Listeria outbreaks can originate from diverse foods, highlighting the need for novel strategies to improve food safety. The first step in Listeria invasion is internalization of the bacteria, which is mediated by the interaction of the internalin family of virulence factors with host cell receptors. A crucial interaction for Listeria invasion of the placenta, and thus a target for therapeutic intervention, is between internalin B (InlB) and the receptor c-Met. Single-domain antibodies (VHH, also called nanobodies, or sdAbs) from camel heavy-chain antibodies are a novel solution for preventing Listeria infections. The VHH R303, R330, and R326 all bind InlB with high affinity; however, the molecular mechanism behind their mode of action was unknown. We demonstrate that despite a high degree of sequence and structural diversity, the VHH bind a single epitope on InlB. A combination of gentamicin protection assays and florescent microscopy establish that InlB-specific VHH inhibit Listeria invasion of HeLa cells. A high-resolution X-ray structure of VHH R303 in complex with InlB showed that the VHH binds at the c-Met interaction site on InlB, thereby acting as a competitive inhibitor preventing bacterial invasion. These results point to the potential of VHH as a novel class of therapeutics for the prevention of listeriosis.

Listeria monocytogenes, a foodborne pathogen and well known causative agent of listeriosis in humans that is also known to form biofilm on utensils used in the dairy industry is well studied for peptide-based Quorum sensing system (agr QS system). In the present study, we are reporting L. monocytogenes strain BN3 to respond to an acyl-homoserine lactone (AHL) by expression of virulence gene (hlyA) and the gene responsible for biofilm formation (srtA) using Real-Time PCR technology. It revealed that in L. monocytogenes, hlyA gene (encodes listeriolysin O) expression increased 0.7-fold in response to 500 nM AHL (C4-HSL treated) as compared to control. Also, in response to 500 nM AHL, (C4-HSL treated) strain BN3 showed 27-fold up-regulation of srtA gene (encodes enzyme sortase) as compared to control. Our study confirmed the cross-talk between Gram-positive and Gram-negative bacteria since L. monocytogenes strain BN3 responds to C4-HSL, which is normally produced by Gram-negative bacteria. Here, we suggest targeting both agr based QS and AHL based QS system together in L. monocytogenes to tackle biofilm formed on milk cans in dairy industries and when treating listeria infections.

Rationale: Listeria monocytogenes (L. monocytogenes) is a compatible intracellular bacterial pathogen that can invade different mammalian cells and reach the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), conventional tests are often reported as negative due to antibiotic therapy or low bacterial content in cerebrospinal fluid. To date, prompt diagnosis and accurate treatment remain a challenge for patients with Listeria infections. Patient concerns: Here, we report a case of a 64-year-old male diagnosed with LMM by using metagenomics next-generation sequencing (mNGS). Diagnosis: LMM was confirmed by mNGS analysis of cerebrospinal fluid. Interventions: The patient was treated with piperacillin and sensitive antibiotics. Outcomes: The patient could walk independently about 1 month after admission and was discharged from the hospital. Lessons: This case highlights the value of mNGS in the diagnosis of LMM and emphasizes the inadequate sensitivity of conventional diagnostic methods for Listeria infection.

Background:Listeria monocytogenes is a gram-positive bacteria that cause the invasive disease listeriosis. Human clinical syndromes are infrequent, mostly appearing in immunosuppressed individuals, newborns, the elderly, pregnant women, and occasionally healthy patients.Objectives:We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections in an immunodepressed population by rheumatic diseases.Methods:Descriptive Observational Study. A retrospective analysis of 143 patients were performed affected by listeriosis, with positive isolation of Listeria monocytogenes from blood, treated in the H.U. Virgen del Rocío (Seville- Spain) between 2003-2019. Of them 9 were rheumatic patients. The type of clinical manifestation was analyzed, paying special attention to the characteristics associated with patients with neurological complications or unfavorable outcome (death and / or abortion in pregnant women), immunosuppression (associated with cancer or rheumatic disease) was assessed as independent variables, chronic diseases (Hypertension, Diabetes Mellitus, dyslipidemia, COPD, Renal Insufficiency and Ischemic Heart Disease) as well as other baseline characteristics of the patient. (age, sex, pregnancy) and their toxic habits (tobacco and alcohol).Results:The sample includes a similar proportion of men (70 cases) and women (73 cases), of all ages. Of the total patients, most (85%) required hospital admission, with a duration median (non-parametric data) of 11 days. 78% of the cases admitted showed a favorable evolution. However, 15.4% resulted in death and 5.6% in abortion. This percentage of abortions represented 29% of the total pregnant women admitted Of all the patients admitted, a third (33%) were immunocompromised, including patiets with cancer (79%) and rheumatic diseases (21%). Include lupus (33%), RA (22%), APs (11%), polymyalgia rheumatica (11%), panuveitis (11%) and ANCA vasculitis MPO specificity (11%). All of them required admission although the majority showed a favorable evolution, except one of the patient. which resulted in death, in which case in addition to lupus he presented with prostate cancer. Regarding the baseline treatment of these patients, 7 underwent treatment with synthetic DMARDs and three with biological DMARDs (1 Adalimumab, 1 Infliximab and 1 Rituximab) As a result of the listeria infection, most of them had fever or digestive symptoms and two of they experienced neurological manifestations (meningoencephalitis) None of these last two (with lupus and RA) had biological DMARDs.Conclusion:Listeriosis is an uncommon but potentially serious infection usually in older people, pregnant women and immunocompromised patients. In our sample, 33% of the patients were immunocompromised. Of the 9 patients. affected by listeria with rheumatic disease we find a death for meningoencephalitis. Given the impact of this infection in immunosuppressed patients should pay attention in our patients with fever and neurological manifestations.Reference:[1]Eleftherios Mylonakis et al. A Case Series and Review of 222 Cases. Medicine 2002; 81: 260-269.[2]Alcoba Lez M et al.Meningitis por Listeria monocytogenes en el adulto en España. Presentación de 10 casos y revisión de la literatura. Rev Clin Esp 2002; 202 (12): 638-643.[3]Eleftherios Mylonakis et al. Central Nervous Sistem Infection with Listeria monocytogenes. 33 Years’ Experience at a General Hospital and Review of 776 Episodes from tha Literature. Medicine 1998; 77: 313-336.Disclosure of Interests:None declared

The C-type lectin member 5A (CLEC5A) is a pattern recognition receptor for members of the Flavivirus family and has critical functions in response to dengue virus and Japanese encephalitis virus. Here we show that CLEC5A is involved in neutrophil extracellular trap formation and the production of reactive oxygen species and proinflammatory cytokines in response to Listeria monocytogenes. Inoculation of Clec5a −/− mice with L. monocytogenes causes rapid bacterial spreading, increased bacterial loads in the blood and liver, and severe liver necrosis. In these mice, IL-1β, IL-17A, and TNF expression is inhibited, CCL2 is induced, and large numbers of CD11b+Ly6ChiCCR2hiCX3CR1low inflammatory monocytes infiltrate the liver. By day 5 of infection, these mice also have fewer IL-17A+ γδ T cells, severe liver necrosis and a higher chance of fatality. Thus, CLEC5A has a pivotal function in the activation of multiple aspects of innate immunity against bacterial invasion., The lectin receptor CLEC5A is a pattern recognition receptor that has been shown to detect dengue and Japanese encephalitis virus. Here the authors show that CLEC5A is needed for optimal ROS production, NET formation and other immune responses to Listeria monocytogenes in mice.

Listeria monocytogenes is transmitted predominantly through contaminated food. About one in seven (14%) cases of Listeria infection occurs during pregnancy. In this study, we assessed the awareness of foodborne pathogens including Listeria and high-risk food consumption, among 218 pregnant women in southeastern Louisiana parishes in and around an urbanized area. The results showed the relationship between awareness of Listeria and selected demographic variables, such as age, race, and education level. The majority (71.1%) of pregnant women reported the consumption of high-risk foods during pregnancy. One person reportedly consumed six of the seven high-risk foods. Gaps existed between awareness of Listeria and high-risk food consumption behaviors, although as pregnant women’s awareness of Listeria increased, their high-risk food consumption behaviors decreased. Targeted continuing education for pregnant women in Louisiana should address the gaps identified in this study.

Listeria monocytogenes is a Gram-positive intracellular bacterium that was transmitted through contaminated food and causes sepsis and even death. IL-37 has been described as an important anti-inflammatory factor, but little is known about the function of IL-37 in host defense against Liseria monocytogenes (Lm) infection. In mice model of systemic infection, we found that mice treated with IL-37 were more sensitive to Lm infection compared with PBS-treated mice. This reduced resistance to Lm in IL-37-treated mice is accompanied with increased bacterial burden and liver damage. Serum levels of colony-stimulating factors were decreased in IL-37-treated mice. IL-37 treatment reduced bactericidal ability of bone marrow derived macrophages (BMDMs) in vitro, which contribute to the inability of IL-37-treated mice to combat Lm infection. Furthermore, increased apoptosis was observed in Lm-infected macrophages treated with IL-37. Increased macrophage apoptosis reduced percentage in liver macrophages was observed in IL-37-treated mice following Lm infection. These results indicate the negative regulatory effect of IL-37 on host resistance during immune defense against Lm.

Background: Cellular glucose uptake may involve either non-concentrative glucose carriers of the GLUT family or Na+-coupled glucose-carrier SGLT1, which accumulates glucose against glucose gradients and may thus accomplish cellular glucose uptake even at dramatically decreased extracellular glucose concentrations. SGLT1 is not only expressed in epithelia but as well in tumour cells and immune cells. Immune cell functions strongly depend on their metabolism, therefore we hypothesized that deficiency of SGLT1 modulates the defence against bacterial infection. To test this hypothesis, we infected wild type mice and gene targeted mice lacking functional SGLT1 with Listeria monocytogenes. Methods: SGLT1 deficient mice and wild type littermates were infected with 1x104 CFU Listeria monocytogenes intravenously. Bacterial titers were determined by colony forming assay, SGLT1, TNF-α, IL-6 and IL-12a transcript levels were determined by qRT-PCR, as well as SGLT1 protein abundance and localization by immunohistochemistry. Results: Genetic knockout of SGLT1 (Slc5a1–/– mice) significantly compromised bacterial clearance following Listeria monocytogenes infection with significantly enhanced bacterial load in liver, spleen, kidney and lung, and significantly augmented hepatic expression of TNF-α and IL-12a. While all wild type mice survived, all SGLT1 deficient mice died from the infection. Conclusions: SGLT1 is required for bacterial clearance and host survival following murine Listeria infection.

The therapeutic use of biological agents such as anti tumor necrosis factor-alpha drugs carries on an increased risk of reactivation of bacterial infections. Among these, listeriosis is a particularly dreadful infection in that may be associated with septic complications such as meningitis and encephalitis and a relatively high mortality rate. This article will discuss listeria infections in patients treated with biological agents.