Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions’ attack by pathogens, including bacteria, viruses, fungi, and parasites.

Formerly a commensal organism of the mucosal surfaces of most healthy individuals, Candida albicans is an opportunistic pathogen that causes infections ranging from superficial to the more life-threatening disseminated infections, especially in the ever-growing population of vulnerable patients in the hospital setting. In these situations, the fungus takes advantage of its host following a disturbance in the host defense system and/or the mucosal microbiota. Overwhelming evidence suggests that the gastrointestinal tract is the main source of disseminated C. albicans infections. Major risk factors for disseminated candidiasis include damage to the mucosal intestinal barrier, immune dysfunction, and dysbiosis of the resident microbiota. A better understanding of C. albicans' interaction with the intestinal epithelial barrier will be useful for designing future therapies to avoid systemic candidiasis. In this review, we provide an overview of the current knowledge regarding the mechanisms of pathogenicity that allow the fungus to reach and translocate the gut barrier.

Candida albicans ( C. albicans ) is an opportunistic pathogen causing infections ranging from superficial to life-threatening disseminated infections. In a susceptible host, C. albicans is able to translocate through the gut barrier, promoting its dissemination into deeper organs. C. albicans hyphae can invade human epithelial cells by two well-documented mechanisms: epithelial-driven endocytosis and C. albicans -driven active penetration. One mechanism by which host cells protect themselves against intracellular C. albicans is termed autophagy. The protective role of autophagy during C. albicans infection has been investigated in myeloid cells; however, far less is known regarding the role of this process during the infection of epithelial cells. In the present study, we investigated the role of autophagy-related proteins during the infection of epithelial cells, including intestinal epithelial cells and gut explants, by C. albicans . Using cell imaging, we show that key molecular players of the autophagy machinery (LC3-II, PI3P, ATG16L1, and WIPI2) were recruited at Candida invasion sites. We deepened these observations by electron microscopy analyses that reveal the presence of autophagosomes in the vicinity of invading hyphae. Importantly, these events occur during active penetration of C. albicans into host cells and are associated with plasma membrane damage. In this context, we show that the autophagy-related key proteins ATG5 and ATG16L1 contribute to plasma membrane repair mediated by lysosomal exocytosis and participate in protecting epithelial cells against C. albicans -induced cell death. Our findings provide a novel mechanism by which epithelial cells, forming the first line of defense against C. albicans in the gut, can react to limit C. albicans invasion.