Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract that are multifactorial in nature. The pathophysiology involves interactions between the host immune system and environmental factors, including the gut microbiota, in genetically predisposed individuals. Advances in understanding these interactions have led to the development of novel therapeutic targets, ranging from anti-TNFα to more recent anti-interleukin 23 treatments.

Deep Characterisation of Circulating Torque Teno Virus DNA Load in Crohn's Disease Patients.

Torque teno virus (TTV) DNA load in plasma is suggested as a marker for immunosuppression post-transplantation. Crohn's disease (CD) arises from genetic susceptibility, environmental factors, and dysbiosis, causing immune responses. This study examines TTV DNA load in CD patients in remission and its correlation with relapse.

Autophagy machinery as exploited by viruses.

Viruses adapt and modulate cellular pathways to allow their replication in host cells. The catabolic pathway of macroautophagy, for simplicity referred to as autophagy, is no exception. In this review, we discuss anti-viral functions of both autophagy and select components of the autophagy machinery, and how viruses have evaded them.

CALCOCO2/NDP52 associates with RAB9 to initiate an antiviral response to hepatitis B virus infection through a lysosomal degradation pathway.

CALCOCO2/NDP52 recognizes LGALS8 (galectin 8)-coated invading bacteria and initiates anti-bacterial autophagy by recruiting RB1CC1/FIP200 and TBKBP1/SINTBAD-AZI2/NAP1. Whether CALCOCO2 exerts similar functions against viral infection is unknown. In our recent study we show that CALCOCO2 targets envelope proteins of hepatitis B virus (HBV) to the lysosome for degradation, resulting in inhibition of viral replication.

Impaired reprogramming of the autophagy flux in maturing dendritic cells from crohn disease patients with core autophagy gene-related polymorphisms.

Crohn disease (CD) is an inflammatory bowel disease whose pathogenesis involves inappropriate immune responses toward gut microbiota on genetically predisposed backgrounds. Notably, CD is associated with single-nucleotide polymorphisms affecting several genes involved in macroautophagy/autophagy, the catabolic process that ensures the degradation and recycling of cytosolic components and microorganisms. In a clinical translation perspective, monitoring the autophagic activity of CD patients will require some knowledge on the intrinsic functional status of autophagy.

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 T lymphocytes.

HIV-1 entry into CD4 T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4 T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown.

NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway.

Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelope proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance.

Use of imaging modalities for decision-making in inflammatory bowel disease.

Cross-sectional magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS) provide valuable and noninvasive information to accurately assess disease activity, severity, and extent; detect complications; and monitor the response to treatment, as well as predict the postoperative recurrence of Crohn's disease and a negative disease course. Therefore, both imaging modalities are emerging as pivotal diagnostic tools to achieve the emerging therapeutic target of transmural healing associated with better disease outcomes. Despite its numerous potential advantages over endoscopy and even MRE and its good availability, IUS is still widely underused to monitor and manage inflammatory bowel disease (IBD) patients and help in making clinical decisions in routine practice.

Relationships of circulating CD4 T cell subsets and cytokines with the risk of relapse in patients with Crohn's disease.

Background And Aims: We aimed to analyze circulating CD4 T cell subsets and cytokines during the course of Crohn's disease (CD).

Methods And Results: CD4 T cell subsets, ultrasensitive C-reactive protein (usCRP), and various serum cytokines (IL-6, IL-8, IL-10, IL-13, IL-17A, IL-23, TNFα, IFNγ, and TGFβ) were prospectively monitored every 3 months for 1 year, using multicolor flow cytometry and an ultrasensitive Erenna method in CD patients in remission at inclusion. Relapse occurred in 35 out of the 113 consecutive patients (31%).

The Relationship between DUGBE Virus Infection and Autophagy in Epithelial Cells.

Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Although displaying mild pathogenic potential, DUGV is genetically related to the Crimean-Congo hemorrhagic fever virus (CCHFV), another orthonairovirus that causes severe liver dysfunction and hemorrhagic fever with a high mortality rate in humans. As we previously observed that CCHFV infection could massively recruit and lipidate MAP1LC3 (LC3), a core factor involved in the autophagic degradation of cytosolic components, we asked whether DUGV infection also substantially impacts the autophagy machinery in epithelial cells. We observed that DUGV infection does impose LC3 lipidation in cultured hepatocytes.

The Autophagy Receptor TAX1BP1 (T6BP) improves antigen presentation by MHC-II molecules.

CD4 T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented by the MHC-II molecules. The pathways leading to endogenous MHC-II presentation remain poorly characterized.

Novel molecular insights into the autophagy-virus arms race.

Autophagy can restrict virus replication so efficiently that viruses have evolved means to avoid or oppose the autophagic response. Two recent studies (Ames et al. and Martin-Sancho et al.

Interactions of Autophagy and the Immune System in Health and Diseases.

Autophagy is a highly conserved process that utilizes lysosomes to selectively degrade a variety of intracellular cargo, thus providing quality control over cellular components and maintaining cellular regulatory functions. Autophagy is triggered by multiple stimuli ranging from nutrient starvation to microbial infection. Autophagy extensively shapes and modulates the inflammatory response, the concerted action of immune cells, and secreted mediators aimed to eradicate a microbial infection or to heal sterile tissue damage.

Lipidation status of single membrane-associated ATG8 proteins.

ATG8 are core autophagy proteins, the lipidated forms of which decorate double-membraned autophagosomes, as well as single-membraned organelles such as endolysosomes. Recent studies from the Florey and Münz laboratories delineate the status of single membrane-associated ATG8 proteins by indicating that their membrane anchoring can involve phosphatidylserine conjugation and their stabilization depends on ATG4 protease inhibition.

Selective Autophagy Receptors in Antiviral Defense.

Autophagy ensures the degradation of cytosolic substrates by the lysosomal pathway. Cargoes destined to be eliminated are confined within double-membrane vesicles called autophagosomes, prior to fusion with endolysosomal vacuoles. Autophagy receptors selectively interact with cargoes and route them to elongating autophagic membranes, a process referred to as selective autophagy.

A novel mutation of PCSK1 responsible for PC1/3 deficiency in two siblings.

Proprotein convertase 1 (PCSK1, PC1/3) deficiency is an uncommon cause of neonatal malabsorptive diarrhoea associated with endocrinopathies that are due to the disrupted processing of a large number of prohormones, including proinsulin. To date, only 26 cases have been reported. Herein, we describe two siblings with typical features including severe congenital diarrhoea, central diabetes insipidus, growth hormone deficiency, and hypoadrenalism.

Low Levels of Fecal Calprotectin 3 Months After Surgery Predict Subsequent Endoscopic Postoperative Remission in Crohn's Disease.

Background/aims: In Crohn's disease (CD) few data are available on the usefulness of monitoring fecal calprotectin (FC) in the early postoperative setting. We assessed prospectively the accuracy of FC measured 3 months after surgery to predict the risk of endoscopic postoperative recurrence (POR) within 1 year after resection.

Methods: In 55 consecutive CD patients who had undergone ileocolonic resection samples were collected 3 months after surgery for measuring serum CRP and FC.

Regulation of anti-microbial autophagy by factors of the complement system.

The complement system is a major component of innate immunity that participates in the defense of the host against a myriad of pathogenic microorganisms. Activation of complement allows for both local inflammatory response and physical elimination of microbes through phagocytosis or lysis. The system is highly efficient and is therefore finely regulated.