Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation.

Early life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory towards health versus disease. Monocytes, macrophages and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin.

Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup.

Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells.

A Novel CovS Variant Harbored by a Colonization Strain Reduces Streptococcus pyogenes Virulence.

Streptococcus pyogenes, also known as group A Streptococcus, causes a wide variety of diseases ranging from mild noninvasive to severe invasive infections. To identify possible causes of colonization-to-invasive switches, we determined the genomic sequences of 10 isolates from five pairs each composed of an invasive strain and a carriage strain originating from five infectious clusters. Among them, one pair displayed a single-nucleotide difference in , encoding the sensor histidine kinase of the two-component CovRS system that controls the expression of 15% of the genome.

FLG Deficiency in Mice Alters the Early-Life CD4 T-Cell Response to Skin Commensal Bacteria.

FLG variants underlie ichthyosis vulgaris and increased risk of atopic dermatitis, conditions typified by disruption of the skin microbiome and cutaneous immune response. Yet, it remains unclear whether neonatal skin barrier compromise because of FLG deficiency alters the quality of commensal-specific T cells and the functional impact of such responses. To address these questions, we profiled changes in the skin barrier and early cutaneous immune response of neonatal C57BL/6 Flg and wild-type mice using single-cell RNA sequencing, flow cytometry, and other modalities.

Intestinal inflammation alters the antigen-specific immune response to a skin commensal.

Resident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4 regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation.

Erdheim-Chester Disease Revealed by Central Positional Nystagmus: A Case Report.

Erdheim-Chester disease (ECD) is a rare histiocytic disorder, recently recognized to be neoplastic. The clinical phenotype of the disease is extremely heterogeneous, and depends on the affected organs, with the most frequently reported manifestations being bone pain, diabetes insipidus and neurological disorders including ataxia. In this article, we report on a case of a 48-year-old woman, whose initial symptom of gait instability was isolated.

Study of the Comorbidity Between Cases of Acute Peripheral Vestibulopathies and COVID-19.

Importance: An infective etiology of acute peripheral vestibulopathy (APV) has long been hypothesized. In the context of coronavirus disease 2019 (COVID-19), we examined the possible comorbidity between these two entities.

Objectives: APV is the second most common cause of vestibular disorders and results from a sudden and unilateral loss of vestibular inputs.

Clinical management of Menière's disease: Clinician perspective in 2020.

Menière's disease (MD) still presents both diagnostic and therapeutic difficulties. Today, this pathology is diagnosed only on clinical criteria. The development of high resolution magnetic resonance imaging of the inner is very promising to improve diagnostic criteria in MD.

Streptococcus pyogenes infects human endometrium by limiting the innate immune response.

Group A Streptococcus (GAS), a Gram-positive human-specific pathogen, yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. Before efficient prophylactic measures were introduced, the mortality rate for mothers during childbirth was approximately 10%; puerperal fever still accounts for over 75,000 maternal deaths annually. Yet, little is known regarding the factors and mechanisms of GAS invasion and establishment in postpartum infection.

Developing Human Skin Contains Lymphocytes Demonstrating a Memory Signature.

Lymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity.

Drug-Induced Hearing Loss in Children: An Analysis of Spontaneous Reports in the French PharmacoVigilance Database.

Introduction: Hearing loss can have a negative impact on communication, with significant vocational, educational, and social consequences. Drugs are one of the causes of hearing loss in children.

Objectives: The objective of our study was to describe drug-induced hearing loss in the pediatric population.

Vestibular disorders: clinician ENT perspective on the need for research and innovation.

Objective: Vertigo and dizziness are a frequent reason for medical consultation. However, diagnostic and therapeutic management is sometimes limited, and clinicians are faced with many unmet needs. The purpose of this study was to identify and prioritize these needs.

Toxin-Triggered Interleukin-1 Receptor Signaling Enables Early-Life Discrimination of Pathogenic versus Commensal Skin Bacteria.

The host must develop tolerance to commensal microbes and protective responses to infectious pathogens, yet the mechanisms enabling a privileged relationship with commensals remain largely unknown. Skin colonization by commensal Staphylococcus epidermidis facilitates immune tolerance preferentially in neonates via induction of antigen-specific regulatory T cells (Tregs). Here, we demonstrate that this tolerance is not indiscriminately extended to all bacteria encountered in this early window.

MAIT cells are imprinted by the microbiota in early life and promote tissue repair.

How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens.

The Molecular Basis of Human IgG-Mediated Enhancement of C4b-Binding Protein Recruitment to Group A Streptococcus.

infects over 700 million people worldwide annually. Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. We recently showed that human IgG increased C4BP binding to the bacterial surface, which promoted streptococcal immune evasion and increased mortality in mice.

In utero drug exposure and hearing impairment in 2-year-old children A case-control study using the EFEMERIS database.

Introduction: As the ear development extends from the 4th to the 30th week of pregnancy, in utero exposure to ototoxic drugs might lead to hearing impairment in the fetus. The main study objective was to assess the association between in utero drug exposure and the occurrence of hearing impairment in 2-year-old children.

Methods And Materials: A case-control study was carried out using the EFEMERIS database, recording medications dispensed during pregnancy and the compulsory health certificates for child at 8 days, 9 and 24 months.

The N-terminal domain of the R28 protein promotes group A adhesion to host cells via direct binding to three integrins.

Group A (GAS) is a human-specific pathogen responsible for a wide range of diseases, ranging from superficial to life-threatening invasive infections, including endometritis, and autoimmune sequelae. GAS strains express a vast repertoire of virulence factors that varies depending on the strain genotype, and many adhesin proteins that enable GAS to adhere to host cells are restricted to some genotypes. GAS is the third most prevalent genotype in invasive infections in France and is associated with gyneco-obstetrical infections.

Human IgG Increases Virulence of through Complement Evasion.

is an exclusively human pathogen that can provoke mild skin and throat infections but can also cause fatal septicemia. This gram-positive bacterium has developed several strategies to evade the human immune system, enabling to survive in the host. These strategies include recruiting several human plasma proteins, such as the complement inhibitor, C4b-binding protein (C4BP), and human (hu)-IgG through its Fc region to the bacterial surface to evade immune recognition.

Control of vertigo in Ménière's disease by intratympanic dexamethasone.

Objective: The main objective was to assess the efficacy of intratympanic dexamethasone injection in controlling vertigo in unilateral Ménière's disease refractory to medical treatment.

Materials And Methods: A retrospective study included 25 patients with disabling unilateral Ménière's disease, defined according to the American Academy of Otorhinolaryngology-Head and Neck Surgery (AAO-HNS) criteria. Patients received intratympanic dexamethasone during the monitoring period.

Complete Genome Sequence of Streptococcus pyogenes emm28 Clinical Isolate M28PF1, Responsible for a Puerperal Fever.

We report the sequence of the Streptococcus pyogenes emm28 strain M28PF1, isolated from a patient with postpartum endometritis. The M28 protein is smaller than that of MGAS6180 (NC_007296.1).

Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.

Streptococcus pyogenes AP1, a strain of the highly virulent M1 serotype, uses exclusively protein H to bind the complement inhibitor C4b-binding protein (C4BP). We found a strong correlation between the ability of AP1 and its isogenic mutants lacking protein H to inhibit opsonization with complement C3b and binding of C4BP. C4BP bound to immobilized protein H or AP1 bacteria retained its cofactor activity for degradation of (125)I-C4b.