A Sweet Response to a Sour Situation: The Role of Soluble Pattern Recognition Receptors in the Innate Immune Response to Invasive Aspergillus fumigatus Infections

Aspergillus spp. infect around 11,000,000 patients, resulting in about 600,000 deaths per year, but these numbers are on the rise due to the emergence of antifungal-resistant strains and a lack of sensitive diagnostic tests [1]. It is increasingly acknowledged that soluble pattern recognition receptors (PRRs), such as the complement component C1q, the collectins (MBL, SP, and CL-11), PTX3, and the ficolins (ficolin-1, 2, 3 and A), are important within anti-Aspergillus immunity [2]. Moreover, studies have highlighted that they may be used as a possible alternative to current antifungal drugs or used in combination to increase efficacy [3]. Binding of pathogen-associated molecular patterns (PAMPs) on the pathogen surface by soluble PRRs often results in opsonisation. This enhances interactions with membrane-associated PRRs on phagocytes, such as the important β-glucan receptor Dectin-1, Toll-like receptors (TLRs), complement receptors (CR1), and Fc receptors; ultimately augmenting phagocytosis, which is essential in controlling the infection [2]. Alternatively, opsonins can promote fungal damage directly or further promote opsonisation by C3b deposition via activation of the conserved complement system [4]. There are three main arms of the complement system, which are the classical, alternative, and lectin pathways. C1q primarily activates the classical antibody-mediated pathway, whereas MBL, CL-11, and the ficolins are known to activate the lectin complement pathway via activation of the mannose-binding lectin-associated serine proteases (MASPs). However, SP-A and SP-D are not involved in complement activation, and the role of CL-11 in Aspergillus immunity is yet to be explored. Furthermore, PTX3 can interact with complement activators and inhibitory components to modulate all three pathways [5]. The role of each of these PRRs in anti-Aspergillus immunity will be discussed further.