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Resume L’endometrite du post-partum est frequente et represente 2 % des infections du post-partum dans les pays a bon niveau socioeconomique. En France, 2,3 % des deces sont imputes aux infections puerperales. Le facteur de risque le plus important est l’accouchement par cesarienne, d’autant plus lorsque celle-ci est effectuee apres le debut du travail. Les bacteries du microbiote vaginal sont associees a l’endometrite du post-partum. Les signes d’appel sont l’apparition de douleurs abdominopelviennes, une hyperthermie, des lochies anormales. Le diagnostic est clinique, confirme par une douleur a la mobilisation uterine. L’antibiotherapie probabiliste de premiere intention est l’amoxicilline–acide clavulanique, 3 a 6 grammes par jour selon le poids par voie intraveineuse ou per os. En cas de contre-indication aux penicillines (anaphylaxie par exemple), l’association clindamycine 600 mg × 4/j plus gentamicine 5 mg/kg × 1/j sera utilisee, elle doit relever d’un avis specialise en cas d’allaitement maternel. Le traitement est poursuivi jusqu’a l’obtention de 48 heures d’apyrexie et la disparition des douleurs provoquees. En cas de persistance de la fievre et/ou des douleurs pelviennes apres 72 heures d’antibiotherapie, une imagerie pelvienne devra etre realisee pour rechercher une retention placentaire, une thrombophlebite pelvienne septique, un abces profond ou tout autre complication chirurgicale, et eliminer les diagnostics differentiels. Il est important de souligner les difficultes d’interpretation des images endo-uterines en echographie. Une heparinotherapie a posologie hypocoagulante doit etre debutee en cas de thrombophlebite pelvienne septique pour une duree de 6 semaines, ou plus s’il existe des complications a type d’embols ou des facteurs de risque thrombotique. Concernant la prevention, lors d’une cesarienne, un badigeonnage vaginal avec de la polividone-iodee ou de la chlorhexidine est recommande avant la cesarienne si possible, et la delivrance du placenta doit etre spontanee.

A 55-year-old woman with an unexplored 1-month history of rectal bleeding presented to the emergency department with abdominal pain, chills, and fever. The patient had received rituximab, a monoclonal antibody targeting the CD20 antigen expressed on B cells, for rheumatoid arthritis. An abdominal

International audience; A recently developed, automated blood culture system and medium improve the timeto-positivity (TTP) for bacteremia. However, there have thus far been no genus-level analyses using this novel system. We evaluated and compared the changes in blood culture TTP between two systems: BacT/Alert 3D with a blood culture medium containing activated charcoal versus the more recent BacT/Alert Virtuo with a blood culture medium containing polymeric beads. This before-and-after study included blood cultures collected between July 2010 and April 2014 (3D, activated charcoal) and between July 2015 and April 2018 (Virtuo, polymeric beads). A total of 554,732 blood cultures were included, 267,935 (48.30%) during the first period and 286,797 (51.70%) during the second period. Overall, 55,611 (10.02%) tested positive for at least one microorganism. The incubation of the blood culture medium in the Virtuo system was associated with reduced TTP for the most prevalent bacteria, those representing 91.72% (n=51,006) of all the positive blood cultures. The median TTP was reduced by 0.99 hours for Staphylococcus, Enterococcus, Streptococcus, Pseudomonadales, and most of the genera within the order Enterobacterales (except the family Morganellaceae). However, strictly anaerobic bacteria belonging to the genus Bacteroides, representing 0.85% (n=474) of all positive blood cultures, were detected 4.53 hours later using the Virtuo system. Virtuo was associated with a shorter TTP for most bacteria, but this improvement was heterogeneous to the genus level.

Objective Low-birthweight infants admitted to neonatal intensive care units are at high risk of hospital-acquired infections by opportunistic pathogens. The gut microbiota of preterm neonates lacks commensal bacteria providing a barrier against pathogens. We report a case of bacteremia due to Kosakonia cowanii in a preterm neonate. Case Report A female baby of 680 g was delivered through a cesarean-section at 28 weeks of gestation due to intrauterine growth retardation and fetal rhythm abnormalities. On day 27, two blood cultures grew gram-negative bacilli in a context of functional ileus. No reliable identification could be obtained using matrix assisted laser desorption ionization-time of flight, biochemical reactions with the VITEK 2 GN ID card, or 16S rDNA sequencing. K. cowanii was finally identified by gyrB sequencing. The source of infection may have been either the central venous catheter or translocation from the gut microbiota. Evolution was favorable after 14 days of cefepime (combined with amikacin for 5 days) and central venous catheter removal. Conclusion K. cowanii is a member of the Enterobacteriaceae family that was recently reclassified from the Enterobacter genus. Human infections due to K. cowanii are scarce and have mainly been associated with traumatic inoculation from plants or transient gut colonization. K. cowanii may be an underestimated opportunistic pathogen in susceptible populations such as preterm neonates.

Graphical abstract Characteristics of host-microbiota interactions in asthmatic children favor asthma attacks and may allow to define asthma endotypes. This knowledge offers promising perspectives to treat asthmatic children using precision medicine, Exacerbations are a main characteristic of asthma. In childhood, the risk is increasing with severity. Exacerbations are a strong phenotypic marker, particularly of severe and therapy-resistant asthma. These early-life events may influence the evolution and be involved in lung function decline. In children, asthma attacks are facilitated by exposure to allergens and pollutants, but are mainly triggered by microbial agents. Multiple studies have assessed immune responses to viruses, and to a lesser extend bacteria, during asthma exacerbation. Research has identified impairment of innate immune responses in children, related to altered pathogen recognition, interferon release, or anti-viral response. Influence of this host-microbiota dialog on the adaptive immune response may be crucial, leading to the development of biased T helper (Th)2 inflammation. These dynamic interactions may impact the presentations of asthma attacks, and have long-term consequences. The aim of this review is to synthesize studies exploring immune mechanisms impairment against viruses and bacteria promoting asthma attacks in children. The potential influence of the nature of infectious agents and/or preexisting microbiota on the development of exacerbation is also addressed. We then discuss our understanding of how these diverse host-microbiota interactions in children may account for the heterogeneity of endotypes and clinical presentations. Finally, improving the knowledge of the pathophysiological processes induced by infections has led to offer new opportunities for the development of preventive or curative therapeutics for acute asthma. A better definition of asthma endotypes associated with precision medicine might lead to substantial progress in the management of severe childhood asthma.

International audience; Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered.

International audience; This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads.

Objective To evaluate clinical practices for ESBL-producing urinary tract infection (UTI) in France. Methods We performed an observational, retrospective, cross-sectional, hospital-based study in 22 pediatric departments of university or secondary care hospitals. We collected data of the last five patients presenting with ESBL-producing UTI in 2012 and the physicians’ therapeutic approach to two case vignettes of acute non-septic ESBL-producing pyelonephritis (7-month-old girl) and cystitis (30-month-old girl). The adequacy of the therapeutic decision was analyzed by a panel of independent infectious disease experts. Results A total of 80 case patients of ESBL-producing UTI were collected: 54 with acute pyelonephritis (mean age: 28 months, female: 66%), of whom 98% received an intravenous ESBL-adapted antibiotic treatment and 55% a two-drug antibiotic therapy. Carbapenems were used in 56% of cases and aminoglycosides in 36%. Of the 26 cystitis patients (mean age: 5 years, female: 73%), 85% were treated with antibiotics, including three intravenously (carbapenems = 2). For the case vignettes, physicians (n = 85) would have treated the pyelonephritis patient with carbapenems (76%) and/or aminoglycosides (68%); 71% would have used a two-drug antibiotic treatment. The cystitis patient would have been treated intravenously by 29% of physicians; 8% would have used a two-drug antibiotic treatment, 16% would have prescribed carbapenems, and 11% aminoglycosides. Antibiotic treatments were deemed appropriate in 37% of cases. Conclusions Antimicrobial treatment for ESBL-producing UTI greatly varies, and carbapenems are excessively prescribed. Specific guidelines for ESBL infections are required.

While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1β maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components.

Objective: Describe the microbiological status during a severe asthma exacerbation and at steady state in preschool children ( Methods: Multicenter prospective study (Hauts-de-France, France). 147 asthmatic children were included during an hospitalization for a severe exacerbation (2015-2018). Phenotype, atopic status, viral status (PCR, nasal swab sample), bacteriological status (culture, induced sputum) were assessed during the exacerbation and at steady state, 8 weeks later. Results: We observed a seasonal distribution of the inclusions (figure). During the exacerbation, a virus was identified in 94% (V+); rhinovirus (RV) in 74% (R+), more frequently in June (95%) and September (82%) (p Conclusion: We confirm a high prevalence of RV infection during asthma exacerbations, frequently associated with bacteria. We now aim at exploring the host immune innate responses to these microorganisms.

BACKGROUND Pneumococcal meningitis (PM) is a serious disease that can rarely recur at a later time after the initial episode. METHODS A retrospective multicenter case-control study was conducted with data for children 18 years of age or younger obtained from the National Observatory of Bacterial Meningitis in Children between January 2001 and September 2015. Cases were all patients with RPM. Each case was matched with 2 randomized controls with a single PM episode in the year of the first episode of PM in the case and born the same year. Case and control data were compared. RESULTS Among the 1634 PM episodes in children 18 years of age or younger, 24 (1.5%) children had RPM. RPM cases were significantly less frequent than single PM cases in winter (27% vs. 48%; P=0.03) and showed significantly less concomitant ear, nose and throat infections when considering the first episode (30% vs. 56%, P = 0.04) and all episodes (28% vs. 56%, P < 0.01). Cerebrospinal fluid leakage was frequent in RPM cases versus controls (83% vs. 10%, P < 0.01), including 25% discovered after the third PM episode. Immune deficiency was absent in cases and present in 15% of controls. Cases and controls did not differ in death rate or neurologic outcome. CONCLUSIONS RPM is rare in children. Cerebrospinal fluid leakage must be considered.

International audience; Clostridium ventriculi (formerly Sarcina ventriculi) is a Gram-positive, obligate anaerobic coccus. Human infections due to this bacterium have rarely been reported, its involvement in the development of gastric ulcers and perforation has been suggested. We present a case of bacteremia due to C. ventriculi following acute colonic pseudo-obstruction.

While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae , a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days.

Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase)., Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase). These genome sequences should help in investigating pathophysiological mechanisms of digestive colonization or infection with these highly resistant bacteria.

International audience; Background: Preterm delivery during pregnancy (

Background Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host’s immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury. Results Ex vivo, Pa secretes clinically relevant kynurenine levels (μM to mM). Pa also secretes kynurenic acid and 3-OH-kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production. Conclusion Pa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host’s tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection. Electronic supplementary material The online version of this article (doi:10.1186/s12866-016-0756-x) contains supplementary material, which is available to authorized users.

International audience; ObjectiveTwo years after the French guidelines, the objective was to assess the feasibility and efficiency of ultrasound-guided trans-vaginal drainage of tubo-ovarian abscesses (TOA) and to study the responsible germs.Material and methodsAll the patients with a larger abscess than 20 mm were included prospectively from May 2011 to July 2014 in the university hospital of Lille.ResultsSixty-nine drainages were performed among 50 patients. Success rate was 94%. No complication occurred. One germ was found in 55% of patients, the TOA was polymicrobian in 20% of cases.ConclusionUltrasound-guided trans-vaginal drainage of TOA is safe and effective with more than 90% of success rate.; ButNotre étude avait pour objectif d’évaluer, 2 ans après les nouvelles recommandations professionnelles, la faisabilité et l’efficacité des ponctions trans-vaginales écho-guidées dans la prise en charge des abcès tubo-ovariens (ATO) et d’étudier les germes responsables.Patientes et méthodesDe mai 2011 à juillet 2014, toutes les patientes présentant un abcès tubo-ovarien de plus de 20 mm ont été inclues de façon prospective, à l’hôpital Jeanne-de-Flandre du centre hospitalier régional universitaire de Lille.RésultatsSoixante-neuf ponctions ont été réalisées chez 50 patientes. Le taux de succès était de 94 %. Aucune complication n’a été observée. Un germe a été mis en évidence chez 55 % des patientes et l’ATO était polymicrobien dans 20 % des cas.ConclusionLe traitement des ATO par ponction trans-vaginale écho-guidée a un taux de succès supérieur à 90 % sans complication observée.

Background and objectives Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL. Patients and methods We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria. Results We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment. Conclusion Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae.

International audience; Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV-related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin-8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota.

Introduction Patients with advanced chronic obstructive pulmonary disease (COPD) are at risk for developing invasive pulmonary aspergillosis. A clinical algorithm has been validated to discriminate colonization from putative invasive pulmonary aspergillosis (PIPA) in Aspergillus-positive respiratory tract cultures of critically ill patients. We focused on critically ill patients with COPD who met the criteria for PIPA. Methods This matched cohort study included critically ill patients with COPD from two university hospital intensive care units (ICUs). We studied the risk factors for PIPA as well as the impact of PIPA on short- and long-term outcomes. Whether PIPA was associated with a pattern of bacterial colonization and/or infection 6 months before and/or during ICU stay was assessed. In addition, antifungal strategies were reviewed. Results Fifty cases of PIPA in critically ill patients with COPD in the ICU were matched with one hundred control patients with COPD. The ICU short- and the long-term (at 1 year) mortality were significantly increased in the PIPA group (p p p = 0.004 and p Conclusions PIPA was a strong death predictor in critically ill patients with COPD. The use of corticosteroids and antibiotics before ICU admission was a risk factor for PIPA. PIPA was not associated with a specific bacterial pattern of colonization or infection. Prompting antifungal treatment in critically ill patients with COPD who have PIPA may not be the only factor involved in prognosis reversal.

International audience; One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.

Background:Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more sensitive than tuberculin skin tests for the detection of infected individuals in dialysis patients.Methods:On 143 dialysis patients prospectively enrolled, we compared the results from the QuantiFERON®-TB Gold assay (QFT), to those of an IGRA in response to in vitro stimulation of circulating mononuclear cells with the mycobacterial latency antigen Heparin-Binding Haemagglutinin purified from Mycobacterium bovis BCG (native HBHA, nHBHA).Results:Seven patients had a past history of active TB and 1 had an undetermined result with both IGRAs. Among the other 135 patients, 94 had concordant results with the QFT and nHBHA-IGRA, 40.0% being negative and therefore not latently infected, and 29.6% being positive and thus LTBI. Discrepant results between these tests were found for 36 patients positive only with the nHBHA-IGRA and 5 only with the QFT.Conclusions:The nHBHA-IGRA is more sensitive than the QFT for the detection of LTBI dialysis patients, and follow-up of the patients will allow us to define the clinical significance of discrepant results between the nHBHA-IGRA and the QFT. © 2013 Dessein et al., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer's patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer's patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3 beta was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer's patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer's patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion.

Background & Aims: The low calcium response V (LcrV) protein synthesized by gram-negative, pathogenic yersiniae participates in bacterial evasion of the host's innate immune response by stimulating synthesis of the anti-inflammatory interleukin (IL)-10 and preventing the activation of proinflammatory cytokines. Methods: We genetically engineered the food-grade bacterium Lactococcus lactis to secrete the LcrV protein from the enteropathogenic species Yersinia pseudotuberculosis . The protective and therapeutic potential of orally administered LcrV-secreting L lactis was evaluated in 2 models of acute experimental colitis (induced by trinitrobenzene sulfonic acid [TNBS] and dextran sodium sulfate [DSS], respectively) in wild-type and knockout mice. Results: Oral administration of LcrV-secreting L lactis led to active delivery of LcrV and induction of IL-10 (via a Toll-like receptor 2–dependent pathway) in the colon and prevented TNBS-induced colitis, in contrast to the L lactis control not producing LcrV. Down-regulation of tissue inflammatory markers correlated well with the reduction in damage to the colonic mucosa. In contrast, TNBS-induced colitis was not prevented in IL-10 −/− mice pretreated with LcrV-secreting L lactis , thus showing that IL-10 is required for LcrV protection. Administration of LcrV-secreting L lactis also proved to be very effective in preventing and treating acute DSS-induced colitis. Conclusions: LcrV-secreting L lactis decreased experimentally induced intestinal inflammation in 2 murine models of colitis. This novel approach highlights the potential of using pathogen-derived immunomodulating molecules in vivo as novel therapeutics for inflammatory bowel diseases.