Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis.

The intestinal epithelium plays critical roles in sensing and integrating dietary and microbial signals. How microbiota and intestinal epithelial cell (IEC) interactions regulate host physiology in the proximal small intestine, particularly the duodenum, is unclear. Using single-cell RNA sequencing of duodenal IECs under germ-free (GF) and different conventional microbiota compositions, we show that specific microbiota members alter epithelial homeostasis by increasing epithelial turnover rate, crypt proliferation, and major histocompatibility complex class II (MHCII) expression. Microbiome profiling identified Faecalibaculum rodentium as a key species involved in this regulation. F. rodentium decreases enterocyte expression of retinoic-acid-producing enzymes Adh1, Aldh1a1, and Rdh7, reducing retinoic acid signaling required to maintain certain intestinal eosinophil populations. Eosinophils suppress intraepithelial-lymphocyte-mediated production of interferon-γ that regulates epithelial cell function. Thus, we identify a retinoic acid-eosinophil-interferon-γ-dependent circuit by which the microbiota modulates duodenal epithelial homeostasis.

Undetected Chikungunya virus co-infections in a Brazilian region presenting hyper-endemic circulation of Dengue and Zika.

BACKGROUND: Chikungunya virus (CHIKV) causes a disease characterized by acute onset of fever accompanied by arthralgia. Clinical similarities and co-circulation of other arboviruses such as Dengue virus (DENV) and Zika virus (ZIKV), have complicated their differentiation, making their diagnoses a challenge for the health authorities. Misdiagnosis is a serious issue to the management of patients and development of public health measures. OBJECTIVES: We carried out further screening of CHIKV, DENV and ZIKV cases in Minas Gerais, Brazil, after diagnostics were already issued by a state laboratory and according to the Brazilian Ministry of Health (BMH) policy. Our aim was to look for possible co-infections or previous arboviruses' exposure. STUDY DESIGN: Sera from 193 patients with symptoms of arboviral infections were tested for DEV, ZKV and/or CHIKV by the State laboratory, according to clinical suspicion and following standard BMH guidelines. After an official diagnosis was issued for each patient, we retested samples applying a broader panel of ELISA-based serological tests. RESULTS: We identified 13 patients with concurrent or consecutive infections (IgM positive for more than one arbovirus), including 11 individuals that were positive for CHIKV and other previously confirmed arbovirus infection. DISCUSSION: Guidelines established in many arbovirus-endemic countries prioritizes the diagnosis of Zika and Dengue and no further analyzes are done when samples are positive for those viruses. As a result, possible cases of co-infections with chikungunya are neglected, which affects the epidemiological assessments of virus circulation, patient management, and the development of public health policies.