Innate Immunity and the Role of Epithelial Barrier During Aspergillus fumigatus Infection

Abstract

Fungi are the most important eukaryotic infective agents in Europe which largely overpass parasite infections. Total number of people dying of fungal infection is increasing and this trend is likely to continue due to the increase in immunosuppressive treatments. The opportunistic pathogen Aspergillus fumigatus (Af) is a saprophytic filamentous fungus that can cause invasive pulmonary diseases in immuno-compromised hosts. In veterinary medicine aspergillosis is also a recurrent problem since it infects various species, birds are particularly susceptible. It propagates through airborne conidia (spores), which are inhaled into the small airways where they may germinate and initiate an infection. The host epithelium has permanent contact with the environment and a multitude of diverse microorganisms, resulting in a network of the host's defense mechanisms. Pathogens use various strategies to invade epithelial barriers, to exploit eukaryotic host function to their own benefit and disseminate throughout the host using the epithelium as a reservoir. The current revue will discuss the ways how epithelial and innate immunity cells can contlol Af infection. We will focus on Af strategies for the host's invasion, antifungal innate immune response and antimicrobial activities of the respiratory epithelial cells.

Fig. (1)

Upon inhalation resting conidia penetrate the alveoli (1) and are entrapped by mucous where (2) they are opsonized by Fikolin-2 which binds directly to 1,3-β-d-glucan, and to a lesser extent by MBP bound to galactomannose. Fikolin-2 bound to Af conidia is fixed additionally by PTX3. This complex is mostly washed out by ciliaric movement into the gut. (3) Some conidia are also grabbed by RAMs residing between ciliaric cells. RAM cells express FcγR able to bind Fikolin-2-PTX3 complex. Besides FcγR, RAMs also express Dectin-1 via direct interaction with surface exposed 1,3-β-d-glucan. This strong interaction induces phagocytosis of Af conidia (4) leading to intracellular digestion. When RAMs face high antigenic load whey start production of toxic molecules (5) like ROS and defensins simultaneously signaling by chemokines and monokines to central innate immune system for help. The major role in case of severe Af infection belongs to PMN (6) which migrate to the infection site and quickly phagocyte Af conidia which at that time germinate.