Complexity and dynamics of host-fungal interactions.

Pathologies attributable to fungal infections represent a growing concern in both developed and developing countries. Initially discovered as opportunistic pathogens of immunocompromised hosts, fungi such as Candida albicans are now being placed at the centre of a more complex and dynamic picture in which the outcome of an infection is the result of an intricate network of molecular interactions between the fungus, the host and the commensal microflora co-inhabiting various host niches, and especially the gastrointestinal (GI) tract. The complexity of the host-fungal interaction begins with the numerous pathogen-associated molecular patterns (PAMPs) present on the fungal cell wall that are recognized by multiple pathogen-recognition receptors (PRRs), expressed by several types of host cells. PAMP-PRR interactions elicit a variety of intracellular signalling pathways leading to a wide array of immune responses, some of which promote fungal clearance while others contribute to pathogenesis. The picture is further complicated by the fact that numerous commensal bacteria normally co-inhabiting the host's GI tract produce molecules that either directly modulate the survival and virulence of commensal fungi such as C. albicans or indirectly modulate the host's antifungal immune responses. On top of this complexity, this host-microbiome-fungal interaction exhibits features of a dynamic system, in which the same fungi can easily switch between different morphological forms presenting different PAMPs at different moments of time. Furthermore, fungal pathogens can rapidly accumulate genomic alterations that further modify their recognition by the immune system, their virulence and their resistance to antifungal compounds. Thus, based on available molecular data alone, it is currently difficult to construct a coherent model able to explain the balance between commensalism and virulence and to predict the outcome of a fungal infection. Here, we review current advances in our understanding of this complex and dynamic system and propose new avenues of investigation to assemble a more complete picture of the host-fungal interaction, integrating microbiological and immunological data under the lens of systems biology and evolutionary genomics.