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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. This situation is clearly due to the absence of validated, reliable, and responsive indices, as well as the lack of trained gastroenterologists and radiologists, as IUS is a component of radiologist expertise in several countries but not yet integrated into the training program of gastroenterologists. However, there is an increasing body of evidence in the literature that IUS and MRE are both becoming essential imaging resources to help clinicians in making reliable decisions. Here, we discuss the up-to-date evidence about the usefulness and performance of cross-sectional imaging, focusing on the ability of bowel US and MRE to aid clinical decision-making for the optimal management and monitoring of IBD.

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. However, some patients still experience resistance to these therapies. Monogenic intestinal diseases (MIDs), which present with more severe symptoms than IBD and typically begin early in life, result from significant disruptions of intestinal homeostasis. MIDs are driven by mutations in a single gene, offering a unique opportunity to explore the mechanisms underlying intestinal homeostasis in health. In this review, we provide a comprehensive overview of the mechanisms of intestinal homeostasis by examining the cellular and molecular features of IBD and MID pathophysiologies.

Autophagy is a biological process that helps cells to recycle obsolete cellular components and which greatly contributes to maintaining cellular integrity in response to environmental stress factors. Autophagy is also among the first lines of cellular defense against invading microorganisms, including viruses. The autophagic destruction of invading pathogens, a process referred to as xenophagy, involves cytosolic autophagy receptors, such as p62/SQSTM1 (Sequestosome 1) or NDP52/CALCOCO2 (Nuclear Dot 52 KDa Protein/Calcium Binding And Coiled-Coil Domain 2), which bind to microbial components and target them towards growing autophagosomes for degradation. However, most, if not all, infectious viruses have evolved molecular tricks to escape from xenophagy. Many viruses even use autophagy, part of the autophagy pathway or some autophagy-associated proteins, to improve their infectious potential. In this regard, the measles virus, responsible for epidemic measles, has a unique interface with autophagy as the virus can induce multiple rounds of autophagy in the course of infection. These successive waves of autophagy result from distinct molecular pathways and seem associated with anti- and/or pro-measles virus consequences. In this review, we describe what the autophagy–measles virus interplay has taught us about both the biology of the virus and the mechanistic orchestration of autophagy.

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. Inactivating NDP52 in hepatocytes results in decreased targeting of viral envelopes in the lysosome and increased levels of viral replication. NDP52 inhibits HBV at both viral entry and late replication stages. In contrast to NDP52-mediated bacterial autophagy, lysosomal degradation of HBV envelopes is independent of galectin 8 and ATG5. NDP52 forms complex with Rab9 and viral envelope proteins and links HBV to Rab9-dependent lysosomal degradation pathway. These findings reveal that NDP52 acts as a sensor for HBV infection, which mediates a unique antiviral response to eliminate the virus. This work also suggests direct roles for autophagy receptors in other lysosomal degradation pathways than canonical autophagy. The nuclear dot protein 52 (NDP52) is an autophagy receptor known to trigger autophagy following bacterial infection. Here, Cui et al. show that NDP52 also triggers an anti-viral response following hepatitis B virus (HBV) infection. NDP52 forms a tripartite complex with Rab9 and envelope proteins of HBV and targets the virus to Rab9-dependent lysosomal degradation pathway.

The interplay between autophagy and intracellular pathogens is intricate as autophagy is an essential cellular response to fight against infections, whereas numerous microbes have developed strategies to escape this process or even exploit it to their own benefit. The fine tuned timing and/or selective molecular pathways involved in the induction of autophagy upon infections could be the cornerstone allowing cells to either control intracellular pathogens, or be invaded by them. We report here that measles virus infection induces successive autophagy signallings in permissive cells, via distinct and uncoupled molecular pathways. Immediately upon infection, attenuated measles virus induces a first transient wave of autophagy, via a pathway involving its cellular receptor CD46 and the scaffold protein GOPC. Soon after infection, a new autophagy signalling is initiated which requires viral replication and the expression of the non-structural measles virus protein C. Strikingly, this second autophagy signalling can be sustained overtime within infected cells, independently of the expression of C, but via a third autophagy input resulting from cell-cell fusion and the formation of syncytia. Whereas this sustained autophagy signalling leads to the autophagy degradation of cellular contents, viral proteins escape from degradation. Furthermore, this autophagy flux is ultimately exploited by measles virus to limit the death of infected cells and to improve viral particle formation. Whereas CD150 dependent virulent strains of measles virus are unable to induce the early CD46/GOPC dependent autophagy wave, they induce and exploit the late and sustained autophagy. Overall, our work describes distinct molecular pathways for an induction of self-beneficial sustained autophagy by measles virus.

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity.

Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales. 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. DUGV infection also caused an upregulation of the MAP1LC3 and SQSTM1/p62 transcript levels, which were, however, more moderate than those seen during CCHFV infection. In contrast, unlike during CCHFV infection, the modulation of core autophagy factors could influence both LC3 lipidation and viral particle production: the silencing of ATG5 and/or ATG7 diminished the induction of LC3 lipidation and slightly upregulated the level of infectious DUGV particle production. Overall, the results are compatible with the notion that in epithelial cells infected with DUGV in vitro, the autophagy machinery may be recruited to exert a certain level of restriction on viral replication. Thus, the relationship between DUGV infection and autophagy in epithelial cells appears to present both similarities and distinctions with that seen during CCHFV infection.

Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO2 and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.