Mucosal-Associated Invariant T Cell Levels Are Reduced in the Peripheral Blood and Lungs of Children With Active Pulmonary Tuberculosis

Mucosal associated invariant T (MAIT) cells are unconventional, semi-invariant T lymphocytes that recognize microbial-derived vitamin B2 (riboflavin) biosynthesis precursor derivatives presented by the monomorphic MHC class 1-related (MR1) molecule. Upon microbial infection, MAIT cells rapidly produce cytokines and cytotoxic effectors, and are thus important players in anti-microbial defense. MAIT cells are protective in experimental models of infection and are decreased in the blood of adult patients with bacterial infections, including Mycobacterium tuberculosis (Mtb). In children, the risk of rapid progression to active tuberculosis (TB) following Mtb infection is higher than in adults. Whether MAIT cells influence the outcome of Mtb infection in children is therefore, an important issue. We analyzed MAIT cell numbers and phenotype in 115 children investigated for pulmonary TB and determined their potential correlation with disease progression. MAIT cells were reduced in numbers and activated in the peripheral blood of children with active TB as compared to those with latent TB infection (LTBI) and healthy children. Moreover, MAIT cells did not accumulate and did not proliferate in the lung of children with active TB. These results suggest that MAIT cells may be important in preventing progression of Mtb infection to active TB in children

Mucosal-Associated Invariant T Cell Interactions with Commensal and Pathogenic Bacteria: Potential Role in Antimicrobial Immunity in the Child

Mucosal-associated invariant T (MAIT) cells are unconventional CD3+CD161high T lymphocytes that recognize vitamin B2 (riboflavin) biosynthesis precursor derivatives presented by the MHC-I related protein, MR1. In humans, their T cell receptor is composed of a Vα7.2-Jα33/20/12 chain, combined with a restricted set of Vβ chains. MAIT cells are very abundant in the liver (up to 40% of resident T cells) and in mucosal tissues, such as the lung and gut. In adult peripheral blood, they represent up to 10% of circulating T cells, whereas they are very few in cord blood. This large number of MAIT cells in the adult likely results from their gradual expansion with age following repeated encounters with riboflavin-producing microbes. Upon recognition of MR1 ligands, MAIT cells have the capacity to rapidly eliminate bacterially infected cells through the production of inflammatory cytokines (IFNγ, TNFα, and IL-17) and cytotoxic effector molecules (perforin and granzyme B). Thus, MAIT cells may play a crucial role in antimicrobial defense, in particular at mucosal sites. In addition, MAIT cells have been implicated in diseases of non-microbial etiology, including autoimmunity and other inflammatory diseases. Although their participation in various clinical settings has received increased attention in adults, data in children are scarce. Due to their innate-like characteristics, MAIT cells might be particularly important to control microbial infections in the young age, when long-term protective adaptive immunity is not fully developed. Herein, we review the data showing how MAIT cells may control microbial infections and how they discriminate pathogens from commensals, with a focus on models relevant for childhood infections

Caractérisation des souches de Escherichia coli responsables de pathologies extra-intestinales chez l'enfant (approche moléculaire et approche clinique)

Pour mieux appréhender les mécanismes physiopathologiques impliqués dans les infections extra-intestinales à E. coli chez l'enfant, nous avons recherché une relation entre les caractéristiques génétiques bactériennes et les facteurs pronostiques cliniques des méningites néonatales et des infections urinaires. Notre stratégie repose sur trois approches : une approche moléculaire globale et ciblée, une approche fonctionnelle associant mutagénèse et modèle de méningite expérimentale et une approche clinique. Nous avons retrouvé une relation négative entre la virulence bactérienne et la mortalité des méningites néonatales, et entre la virulence et les anomalies anatomiques lors des pyélonéphrites. La relation négative entre virulence et résistance aux quinolones n'a pas été retrouvée dans le modèle animal. Enfin nous avons mis en évidence l'émergence d'un clone O45 : K1 hautement virulent, responsable de méningites en France et la présence d'un domaine génétique semblable à l'îlot de pathogénicité PAA IIJ96 dans la souche archétype C5.To understand the pathogenesis of extra-intestinal E. coli in meningitis and urinary tract infections in children, we used a molecular, experimental model and clinical approach. We found a negative association between virulence and lethal outcome in neonatal meningitis as between virulence and anatomical abnormalities in urinary tract infections. The link between genetic virulence and in vitro resistance to quinolones was not proved in the neonatal meningitis rat model. Among our collection of French E. coli neonatal meningitis we identified a major highly virulent O45 : K1 clonal group. The archetypal strain C5 causing neonatal meningitis harbors a pathogenicity island similar to the PAI IIJ96.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

A Uropathogenicity Island Contributes to the Pathogenicity of Escherichia coli Strains That Cause Neonatal Meningitis

We report that the archetypal Escherichia coli strain C5 causing neonatal meningitis harbors a pathogenicity island (PAI) designated PAI I(C5) that is similar to the PAI II(J96) of uropathogenic E. coli J96 inserted in the leuX-tRNA gene. PAI-negative C5 mutants had a lower capacity than C5 to induce high-level bacteremia in a neonatal rat model. However, no change in their resistance to the bactericidal effect of serum and their capacity to cross the blood-brain barrier was observed

Comparative Prevalence of Virulence Factors in Escherichia coli Causing Urinary Tract Infection in Male Infants with and without Bacteremia

Escherichia coli isolates causing urinary tract infection in 83 male infants younger than 90 days with and without bacteremia were compared for phylogenetic groups and the presence of 10 virulence factors. Our result suggest that the absence of both hemolysin and antigen K1 may be used as a negative predictive factor for bacteremia

Culture-Negative Pericarditis Caused by Neisseria meningitidis Serogroup C

We describe a case of primary purulent culture-negative pericarditis caused by Neisseria meningitidis serogroup C occurring in an 8-month-old previously healthy boy, which was detected in pericardial fluid by broad-spectrum PCR amplification

Moving the Dial on Airway Inflammation in Response to Trikafta® in Adolescents with Cystic Fibrosis

International audienceNo abstract availabl

Usefulness of bronchoalveolar lavage in a French pediatric cohort with hypersensitivity pneumonitis

International audienceHypersensitivity pneumonitis (HP) is a rare interstitial lung disease in children, and very little data are available on the frequency, diagnosis, and outcomes of HP. In a pediatric cohort with HP, the characteristics of the CD4/CD8 lymphocyte ratio are often described as nonspecific

Lung sarcoidosis in children: update on disease expression and management

International audienceBackground: Sarcoidosis is a rare lung disease in children. The aim of the present study was to provide update information on disease presentation and progression, patient management and prognosis factors in a cohort of children with lung sarcoidosis.Methods: With the network of the French Reference Centre for Rare Lung Diseases (RespiRare), we collected information on a large cohort of paediatric thoracic sarcoidosis to provide information on disease presentation, management and outcome.Results: Forty-one patients were included with a median age at diagnosis of 11.8 years (1.1-15.8), mostly from Afro-Caribbean and Sub-Saharan origin. At diagnosis, 85% presented with a multi-organic disease, and no major differences were found regarding disease severity between the patients diagnosed before or after 10 years old. Corticosteroids were the most used treatment, with more intravenous pulses in the youngest patients. The 18-month outcome showed that patients diagnosed before 10 years old were more likely to recover (50% vs 29%), and presented fewer relapses (29% vs 58%). At 4-5 years of follow-up, relapses were mostly observed for patients diagnosed after 10 years old.Discussion: In the included children, mostly of Afro-Caribbean and Sub-Saharan origin, sarcoidosis seems severe, with multi-organic involvement and foreground general symptoms. Common prognosis factors are not suitable in paediatric patients, and a young age at diagnosis does not seem to be associated with a poorer prognosis. The study is ongoing to provide further information on the very-long-term follow-up of paediatric sarcoidosis