Figure 1.

Candida albicans at the intestinal barrier: from colonization to translocation and dissemination. a) C. albicans can be found in both the yeast and hyphal morphotypes during colonization of the GI tract of healthy individuals and must compete with other members of the microbiota b) Translocation via M cells present in intestinal lymphoid tissues like Peyer’s patches may occur following either induced endocytosis or active penetration by C. albicans and may also involve the fungus hijacking the sampling function of resident phagocytes, like dendritic cells c) The paracellular route of translocation refers to invasion of the intestinal barrier by C. albicans hyphae in the spaces between enterocytes without actually invading the host cells d) The transcellular route of translocation could occur in two manners: with candidalysin (CaL)-dependent damage of the epithelial cells resulting in necrotic cell death (left) or in the absence of host-cell damage (right) This appears to be the major route used by C. albicans to cross the intestinal barrier e) One hypothesis for how yeast reach the bloodstream is that they are able to move across the epithelial barrier from the GI tract to the bloodstream via physical disruptions in the tissue, caused either by the fungus itself or some other factors like surgery or chemotherapy f) The so-called “hitchhiking” hypothesis posits that yeast present in the GI tract may move through the barrier along with invading hyphae by attaching to them as they invade the epithelium g) Finally, the hypha-to-yeast switch hypothesizes that translocating hyphae undergo a morphological transition once reaching the bloodstream that initiates the formation of yeast cells from the hyphae.