Candida albicansis able to use M cells as a portal of entry across the intestinal barrierin vitro

Abstract

Candida albicans is the most frequent yeast responsible for systemic infections in humans. These infections mainly originate from the gastrointestinal tract where C. albicans can invade the gut epithelial barrier to gain access to the bloodstream. Along the gut, pathogens can use Microfold (M) cells as a portal of entry to cross the epithelial barrier. M cells are specialized cells mainly located in the follicule-associated epithelium of Peyer patches. In this study, we used scanning electron and fluorescence microscopy, adhesion and invasion assays and fungal mutants to investigate the interactions of C. albicans with M cells obtained in an established in vitro model whereby enterocyte-like Caco-2 cells co-cultured with the Raji B cell line undergo a phenotypic switch to morphologically and functionally resembling M cells. Our data demonstrate that C. albicans co-localizes with and invades preferentially M cells, providing evidence that the fungus can use M cells as a portal of entry into the intestinal barrier. In addition to active penetration, F-actin dependent endocytosis contributes to internalization of the fungus into M cells through a mechanism involving hypha-associated invasins including Ssa1 and Als3.

Setting off the Alarms:Candida albicansElicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer’s Patches

“…We found that C. albicans strains ATCC18804 and SC5314, as well as C. tropicalis , were able to cross the intestinal epithelial barrier, and that uptake was partly dependent on M-cells. These findings were supported by Albac et al, who demonstrated C. albicans strain SC5314 uses M-cells as a portal of entry into the intestinal barrier (16, 17). C. albicans was able to preferentially invade M-cells via actin-mediated endocytosis rather than active penetration (16, 17).…”

“…These findings were supported by Albac et al, who demonstrated C. albicans strain SC5314 uses M-cells as a portal of entry into the intestinal barrier (16, 17). C. albicans was able to preferentially invade M-cells via actin-mediated endocytosis rather than active penetration (16, 17). In addition to its ability to cross the epithelial barrier, we also found that C. albicans was sampled by a subset of SED CD11c + phagocytes that expressed the C-type lectin Langerin (16).…”

“…M-cells are important in the controlled transcytosis of luminal antigens and microbes. We and others previously reported that C. albicans ’ translocation into PPs was partially M-cell dependent (16, 17, 27-30). It has been shown that the Rorc deficiency plays a role in susceptibility to Candida sp.…”

Extracellular Vesicle-Associated Transitory Cell Wall Components and Their Impact on the Interaction of Fungi with Host Cells

“…Furthermore, SSA1 appears to act as an invasin contributing to C. albicans virulence in hematogenously disseminated and oropharyngeal candidiasis ( Sun et al, 2010 ). In addition, SSA1 contributes at least partially to C. albicans penetration to microfold-like cells generated by the co-culture of enterocytes with B lymphocytes ( Albac et al, 2016 ). Thus, proteins carried by C. albicans EVs can have opposite effects when in contact with host cells.…”

Membrane Transport across Polarized Epithelia

“…Epstein–Barr virus (EBV) appears to cross oral epithelial cells bidirectionally (Tugizov et al 2013), and HIV transport across polarized epithelial cells may depend on IgG and trafficking by FcRn (Dohgu et al 2011; Gupta et al 2013; Kinlock et al 2014). Candida albicans co-opts the transcytotic pathway of M cells as a portal of entry across the intestinal barrier (Albac et al 2016). Human melanotransferrin (MTf, also named P97), a transferrin homolog undergoes basolateral to apical transcytosis and directs adeno-associated virus (AAV) transcytosis across the blood–brain barrier (Tang et al 2007).…”