Host immune response against fungal biofilms

Abstract

Fungal biofilms are a multilayered community of cells attached to mucosal or abiotic surfaces enclosed in a coating of self-produced extracellular polymeric matrix. The sheer density of cells protected by a polymeric shield not only makes the biofilm impermeable to antimicrobials or immune cells but also hidden from host recognition. Biofilms also serve as a reservoir of drug-resistant persister cells and dispersal cells armored with virulence factors adept at evading the immune system. Here, we summarize the latest knowledge on the immunomodulatory properties of biofilms formed by Candida species and by other biofilm-forming fungal pathogens such as Aspergillus and Cryptococcus. Finally, we deliberate on promising strategies to help activate the immune system for combating fungal biofilms.

Figure 1:

Fungal biofilms are invincible due to production of a thick extracellular polymeric matrix (ECM). Destruction of this protective shield is paramount to generate anti-biofilm immune response and enhance the efficacy of antifungal drugs. A. ECM is a physical barrier that blocks antifungal drug activity and causes drug sequestration; ECM masks fungal PAMPs, contains eDNA/RNA, secreted metabolites and EVs that paralyze phagocytosis, block NETosis, and silence the immune response. B. Disruption of ECM by anti-EV drugs such as turbinmycin, or exposure of PAMPS by echinocandins can help antifungal penetration and immune cell infiltration inside the biofilms, thereby further activating the inflammatory immune system to cause phagocytosis and NETosis.