A Framework for Understanding the Evasion of Host Immunity by Candida Biofilms

Josselyn E. Garcia-Perez, Lotte Mathé, Stephanie Humblet-Baron, Annabel Braem, Katrien Lagrou, Patrick Van Dijck, Adrian Liston

Candida biofilms are a major cause of nosocomial morbidity and mortality. The mechanism by whichCandidabiofilms evade the immune system remains unknown. In this perspective, we develop a theoretical framework of the three, not mutually exclusive, models, which could explain biofilm evasion of host immunity. First, biofilms may exhibit properties of immunological silence, preventing immune activation. Second, biofilms may produce immune-deviating factors, converting effective immunity into ineffective immunity. Third, biofilms may resist host immunity, which would otherwise be effective. Using a murine subcutaneous biofilm model, we found that mice infected with biofilms developed sterilizing immunity effective when challenged with yeast formCandida. Despite the induction of effective anti-Candidaimmunity, no spontaneous clearance of the biofilm was observed. These results support the immune resistance model of biofilm immune evasion and demonstrate an asymmetric relationship between the host and biofilms, with biofilms eliciting effective immune responses yet being resistant to immunological clearance.