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1.
Gynecol Obstet Fertil Senol ; 50(6): 486-493, 2022 06.
Article in French | MEDLINE | ID: mdl-35483610

ABSTRACT

Many countries with a high perinatal level have started a policy of vaccination of pregnant women against pertussis. To date, France has not chosen this policy. The objective was to review knowledge on pertussis mortality in infants. Compare the strategies available to protect the infant before his first vaccination, scheduled for two months of age. We proceeded to a litterature analysis, from January 1998 to 2021. Search by the following keywords used ; "Whooping cough, vaccination, pregnancy, strategy, cocooning", on the scientific basis of "Pubmed", as well as French and foreign vaccination recommendations. Currently 90% of whooping cough deaths are concerning infants under six months of age and this mortality represents 2% of mortality in the first year of life. Vaccination at birth is not effective. The cocooning strategy, which consists of vaccinating those around the child, is expensive and difficult to implement. A systematic vaccination policy for pregnant women is effective and reasonably expensive when compared to the cocooning strategy. In England, it was recently accompanied by a 78% reduction in confirmed cases of pertussis in infants under six months of age. In conclusion, compared to cocooning strategy, pertussis vaccination of pregnant women appears more effective and cost-effective, and this with each pregnancy.


Subject(s)
Whooping Cough , Child , Cost-Benefit Analysis , Female , Humans , Infant , Infant, Newborn , Parturition , Pregnancy , Pregnant Women , Vaccination , Whooping Cough/prevention & control
2.
J Hosp Infect ; 118: 48-58, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34492304

ABSTRACT

Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated.


Subject(s)
Gastrointestinal Microbiome , Pharmaceutical Preparations , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Dysbiosis , Humans
3.
Gynecol Obstet Fertil Senol ; 49(7-8): 608-616, 2021.
Article in French | MEDLINE | ID: mdl-33434747

ABSTRACT

Chlamydia trachomatis (CT) is the most common sexually transmitted bacterial infection worldwide. It is asymptomatic in most cases and mainly affects young women, with potential long term sequelae (pelvic inflammatory disease, tubal infertility, obstetric complications). The impact on male fertility is controversial. Screening methods as well as antibiotics use have recently been reassessed due to resistance phenomena and the negative effect on the urogenital microbiota. Positive CT serology may be indicative of tuboperitoneal pathology, which may not be noticed on hysterosalpingography. New research on single-nucleotide polymorphisms (SNPs) aims to establish a patient profile at higher risk of infectious tubal damage due to CT. CT seropositivity is also associated with decreased spontaneous pregnancy rates and is a predictive factor for obstetrical complications.


Subject(s)
Chlamydia Infections , Infertility, Female , Infertility , Pelvic Inflammatory Disease , Chlamydia Infections/complications , Chlamydia Infections/diagnosis , Chlamydia trachomatis , Female , Humans , Hysterosalpingography , Infertility, Female/etiology , Male , Pregnancy
4.
J Hosp Infect ; 106(3): 500-503, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32745588

ABSTRACT

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.


Subject(s)
Enterobacteriaceae Infections/prevention & control , Enterobacteriaceae/physiology , Infection Control/methods , Intensive Care Units/statistics & numerical data , Rectum/microbiology , Aged , Carrier State/epidemiology , Cross Infection/epidemiology , Enterobacteriaceae/enzymology , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/transmission , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , beta-Lactamases
5.
Gynecol Obstet Fertil Senol ; 47(5): 442-450, 2019 05.
Article in French | MEDLINE | ID: mdl-30890463

ABSTRACT

Postpartum endometritis accounts for 2% of postpartum infections in developed countries. In France, 2.3% of deaths are attributed to puerperal infections. The most important risk factor is cesarean delivery, especially if it is done after the start of labor. Bacteria of the vaginal microbiota are associated with postpartum endometritis. Symptoms are abdomino-pelvic pain, hyperthermia and abnormal lochia. The diagnosis is confirmed by uterine mobilization pain. The first-line antibiotic therapy is amoxicillin-clavulanic acid 3 to 6 grams per day depending on the weight, intravenously or orally. In case of impossibility to use penicillins (anaphylaxis for example), the combination of clindamycin 600mg×4/d plus gentamicin 5mg/kg×1/d may be use, it must be a specialized decision in case of maternal breastfeeding. The treatment is continued until obtaining 48hours of apyrexia and the disappearance of pelvic pain. In case of persistence of fever and/or pelvic pain after 72hours of antibiotic therapy, pelvic imaging should be performed for placental retention, septic thrombophlebitis, deep abscess or any other surgical complication and eliminate differential diagnoses. It is important to highlight the difficulties of interpreting endo-uterine images in ultrasound. Hypocoagulant heparin therapy should be started in case of septic thrombophlebitis for 6 weeks, or longer if there are complications such as embolism or thrombotic risk factors. Regarding prevention, during a caesarean section, a vaginal swab with iodinated polividone or chlorhexidine is recommended before caesarean if possible, and extraction of the placenta must be spontaneous.


Subject(s)
Endometritis , Pelvic Inflammatory Disease , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Cesarean Section/adverse effects , Endometritis/diagnosis , Endometritis/drug therapy , Endometritis/microbiology , Female , Fever , Humans , Pelvic Inflammatory Disease/diagnosis , Pelvic Inflammatory Disease/drug therapy , Pelvic Inflammatory Disease/microbiology , Pelvic Pain , Postoperative Complications/diagnosis , Postoperative Complications/drug therapy , Pregnancy , Puerperal Infection , Risk Factors , Thrombophlebitis/diagnosis , Thrombophlebitis/drug therapy , Vagina/microbiology
6.
Med Mal Infect ; 48(3): 193-201, 2018 May.
Article in English | MEDLINE | ID: mdl-29449049

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae/isolation & purification , Urinary Tract Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Antimicrobial Stewardship , Bacterial Proteins/analysis , Carbapenems/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Cystitis/drug therapy , Cystitis/microbiology , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Female , France/epidemiology , Hospitals, University/statistics & numerical data , Humans , Inappropriate Prescribing , Male , Practice Patterns, Physicians' , Pyelonephritis/drug therapy , Pyelonephritis/microbiology , Retrospective Studies , Secondary Care Centers/statistics & numerical data , Surveys and Questionnaires , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology , beta-Lactam Resistance , beta-Lactamases/analysis
7.
Clin Microbiol Infect ; 23(8): 576.e1-576.e5, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28192236

ABSTRACT

OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.


Subject(s)
Bacteremia/etiology , Bacteremia/immunology , Complement System Proteins/deficiency , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/diagnosis , Meningitis, Bacterial/etiology , Meningitis, Bacterial/immunology , Adolescent , Adult , Female , Humans , Immunologic Factors/deficiency , Male , Mass Screening/methods , Prevalence , Retrospective Studies , Young Adult
8.
Med Mal Infect ; 46(4): 215-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27210283

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cefoxitin/therapeutic use , Escherichia coli Infections/drug therapy , Urinary Tract Infections/drug therapy , beta-Lactam Resistance , Anti-Bacterial Agents/adverse effects , Bacterial Proteins/metabolism , Cefoxitin/adverse effects , Drug Eruptions/etiology , Female , Humans , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Male , Middle Aged , Prospective Studies , Treatment Outcome , Uropathogenic Escherichia coli/drug effects , Uropathogenic Escherichia coli/enzymology , beta-Lactamases/metabolism
9.
Epidemiol Infect ; 144(3): 607-11, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26234410

ABSTRACT

The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of pneumococcal meningitis (PM) in children is unknown. To determine this impact, a descriptive multicentre retrospective cohort study was conducted from 2008 to 2013 in northern France. All laboratory-confirmed PM in children aged <18 years in all hospitals of the area with paediatric units were included. Two independent databases were used for exhaustive identification of cases: medical plus laboratory records at each hospital and discharge codes. The corrected incidence of PM was determined by a capture-recapture analysis using these two databases. Sixty-two cases were found over the 6-year period. A decrease of the PM corrected incidence was observed in the global population (P = 0·07), significant only for children aged <2 years, from 11·9/100 000 in 2008 in 1·9/100 000 in 2013 [6·4 fold-decrease, 95% confidence interval (CI) 1·4-41, P = 0·01] between years 2008 and 2013. When comparing the pre- and post-PCV13 periods, this decrease was still statistically significant for children aged <2 years [7·32/100 000 (95% CI 4·39-10·25) to 2·78/100 000 (95% CI 0·96-4·60), P = 0·01]. Only three (5%) cases of PM caused by vaccine serotypes could have been prevented. After the introduction of the PCV13 vaccine, a decrease in the incidence of PM cases in children in northern France was observed.


Subject(s)
Meningitis, Pneumococcal/epidemiology , Meningitis, Pneumococcal/prevention & control , Pneumococcal Vaccines , Streptococcus pneumoniae/classification , Child , Child, Preschool , Databases, Factual , Female , France/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Interrupted Time Series Analysis , Male , Retrospective Studies , Serogroup , Vaccines, Conjugate
10.
J Gynecol Obstet Biol Reprod (Paris) ; 45(3): 243-8, 2016 Mar.
Article in French | MEDLINE | ID: mdl-26096351

ABSTRACT

OBJECTIVE: Two 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 METHODS: All the patients with a larger abscess than 20mm were included prospectively from May 2011 to July 2014 in the university hospital of Lille. RESULTS: Sixty-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. CONCLUSION: Ultrasound-guided trans-vaginal drainage of TOA is safe and effective with more than 90% of success rate.


Subject(s)
Abscess/therapy , Drainage/methods , Fallopian Tube Diseases/therapy , Ovarian Diseases/therapy , Ultrasonography, Interventional/methods , Abscess/epidemiology , Abscess/microbiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Drainage/adverse effects , Fallopian Tube Diseases/epidemiology , Fallopian Tube Diseases/microbiology , Feasibility Studies , Female , Humans , Middle Aged , Ovarian Diseases/epidemiology , Ovarian Diseases/microbiology , Postoperative Complications/epidemiology , Treatment Outcome , Ultrasonography, Interventional/adverse effects , Vagina/diagnostic imaging , Vagina/microbiology , Young Adult
11.
Arch Pediatr ; 22(1): 24-31, 2015 Jan.
Article in French | MEDLINE | ID: mdl-25482995

ABSTRACT

OBJECTIVE: To determine the rate of therapeutic management satisfying the institutional protocol for children with urinary tract infection (UTI) in the context of the emergence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. METHODS: A retrospective, single-center, observational study was carried out for 1 year (2010-2011). Data from all children admitted to the emergency department with a diagnosis of UTI were analysed. Adherence to the protocol was evaluated for the initial management and at re-evaluation with the definitive result of the urine culture. Risk factors for nonadherence were analysed. RESULTS: Among the children, 393 were included. An ESBL Enterobacteriaceae-related UTI was identified in 2.2% of urine analyses. The initial therapeutic management satisfied the protocol for 95% of children and at re-evaluation for 80%. Nonadherence was related to poorly adapted treatment (59%) and an erroneous indication of dual antibiotic therapy (20%). Variables associated with the inadequacy of the initial management were age less than 3 months (adjusted OR [aOR]: 9.3; 95%CI: 3.5-24.8) and at re-evaluation age under 3 months (aOR: 12.8; 95%CI: 5.5-29.9) and an unconfirmed infection in the final urine culture (aOR: 30.8; 14.7-64.3). CONCLUSION: Adherence to the protocol was good but could be increased by a better re-evaluation procedure with the result of the urine culture. ESBL Enterobacteriaceae-related UTIs were still rare enough to influence the efficacy of management.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology , Adolescent , Age Factors , Child , Child, Preschool , Clinical Protocols , Female , France , Guideline Adherence , Humans , Infant , Infant, Newborn , Male , Patient Compliance , Practice Guidelines as Topic , Retrospective Studies , Urinary Tract Infections/diagnosis
12.
Med Mal Infect ; 43(4): 146-51, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23622953

ABSTRACT

Pseudomonas aeruginosa and Candida albicans are frequently coexisting opportunistic pathogens, responsible for colonization and infection in predisposed patients. They share a virulence specificity relying on auto-inducing, cell density-dependent molecules named quorum-sensing (QS). C. albicans virulence depends on its QS that influences morphological switch from yeast to filamentous form. Similarly, the production of P. aeruginosa virulence factors depends partly on QS molecules. Interactions have been investigated and demonstrated in vitro. P. aeruginosa may kill C. albicans either by producing toxins, such as pyocyanin, or by direct contact on its biofilm-dependent filamentous form. Cross-kingdom communication is a more subtle interaction: C. albicans can adapt its morphology in the presence of P. aeruginosa QS molecules, and inhibit P. aeruginosa QS-dependent virulence factor secretion, through farnesol, one of its QS molecule. But the in vivo relevance of these interactions is still controversial, as models of airway colonization/infection by C. albicans followed by subsequent P. aeruginosa pneumonia give contradictory results, suggesting the probable involvement of the immune system as a third party player. Finally, the authors of clinical studies performed in ventilated patients, indicate that C. albicans colonization could be a risk factor for P. aeruginosa pneumonia. The clinical outcome of C. albicans and P. aeruginosa interaction is uncertain, the virulence modulation demonstrated in these interactions opens new possibilities for future anti-infectious therapeutics.


Subject(s)
Candida albicans/pathogenicity , Candidiasis/microbiology , Opportunistic Infections/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/pathogenicity , Biofilms , Candida albicans/ultrastructure , Coinfection , Host-Pathogen Interactions , Humans , Quorum Sensing/physiology , Virulence/physiology
13.
Med Mal Infect ; 42(3): 126-8, 2012 Mar.
Article in French | MEDLINE | ID: mdl-22341663
14.
Pathol Biol (Paris) ; 60(5): e41-4, 2012 Oct.
Article in French | MEDLINE | ID: mdl-21831534

ABSTRACT

OBJECTIVES: The double-disk synergy test was compared to the Mastdiscs™ ID AmpC and ESßL method for detection of ESßL production in rectal swab. METHODS: Two hundred and forty-nine rectal swabs were directly inoculated onto Mueller-Hinton plates and analyzed according to both methods. RESULTS: A total of 41 (16%) and 208 (84%) were positive and negative for ESßL, respectively. Twelve (29%) and 20 (49%) of the 41 rectal swabs positive for ESßL were detected after 24h of incubation with the double-disk synergy test and the Mastdiscs™ method, respectively (P=0.013). One hundred fifty-eight (76%) et 183 (88%) of the 208 rectal swabs were detected negative for ESßL after 24h of incubation with the double-disk synergy test and the Mastdiscs™ method, respectively (P<0.001). Finally, 79 (32%) and 46 (18%) rectal swabs respectively inoculated according to the double-disk synergy test and the Mastdiscs™ method were inconclusive after 24h of incubation. The better performance of the Mastdiscs™ method was due to an easier detection of cephalosporinase producing bacteria. CONCLUSIONS: The Mastdiscs™ method is a simple phenotypic method that detects more easily ESßL and non-ESßL producing bacteria in rectal swab.


Subject(s)
Bacterial Proteins/biosynthesis , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae/isolation & purification , Microbiological Techniques/methods , Rectum/microbiology , beta-Lactamases/biosynthesis , Drug Resistance, Multiple, Bacterial/genetics , Enterobacter/growth & development , Enterobacter/isolation & purification , Enterobacteriaceae/metabolism , Enterobacteriaceae Infections/microbiology , Humans , Klebsiella/growth & development , Klebsiella/isolation & purification , Microbial Sensitivity Tests , Microbiological Techniques/instrumentation , Reagent Kits, Diagnostic
16.
Gut ; 58(6): 771-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19174417

ABSTRACT

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.


Subject(s)
Peyer's Patches/microbiology , Proteins/metabolism , Signal Transduction/physiology , Toll-Like Receptor 2/metabolism , Yersinia pseudotuberculosis Infections/metabolism , Yersinia pseudotuberculosis , Animals , Cell Line , Epithelial Cells/metabolism , Epithelial Cells/ultrastructure , Female , Gene Deletion , Gene Expression Profiling/methods , Germ-Free Life , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron, Transmission , Nod2 Signaling Adaptor Protein/genetics , Nod2 Signaling Adaptor Protein/metabolism , Pancreatitis-Associated Proteins , Peyer's Patches/metabolism , Peyer's Patches/ultrastructure , Reverse Transcriptase Polymerase Chain Reaction/methods , Toll-Like Receptor 2/genetics
17.
Gastroenterol Clin Biol ; 33 Suppl 3: S131-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-20117336

ABSTRACT

Besides its role in repelling enteropathogenic infections, the gastrointestinal tract is in intimate contact with commensal microbiota. Tremendous advances have been made in determining the pivotal role of the microbiota in both tissue homeostasis and metabolism, as well as in the initiation and maintenance of inflammatory lesions in inflammatory bowel diseases. A better understanding of human gut microbiota could provide innovative targets for treating and/or curing such common immunopathologies of the gastrointestinal tract.


Subject(s)
Bacteria/metabolism , Gastrointestinal Tract/microbiology , Inflammatory Bowel Diseases/microbiology , Metagenome , Gastrointestinal Tract/immunology , Humans , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/therapy , Probiotics/therapeutic use
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