Abstract
The ubiquitous mold Aspergillus fumigatus is the major etiologic agent of invasive aspergillosis, a life-threatening infection amongst immune compromised individuals. An increasing body of evidence indicates that effective disposal of A. fumigatus requires the coordinate action of both cellular and humoral components of the innate immune system. Early recognition of the fungal pathogen, in particular, is mediated by a set of diverse soluble pattern recognition molecules (PRMs) that act as “ancestral antibodies” inasmuch as they are endowed with opsonic, pro-phagocytic and killing properties. Pivotal is, in this respect, the contribution of the complement system, which functionally cooperates with cell-borne pattern recognition receptors (PRRs) and other soluble PRMs, including pentraxins. Indeed, complement and pentraxins form an integrated system with crosstalk, synergism, and regulation, which stands as a paradigm of the interplay between PRMs in the mounting and orchestration of antifungal immunity. Following upon our past experience with the long pentraxin PTX3, a well-established immune effector in the host response to A. fumigatus, we recently reported that this fungal pathogen is targeted in vitro and in vivo by the short pentraxin Serum Amyloid P component (SAP) too. Similar to PTX3, SAP promotes phagocytosis and disposal of the fungal pathogen via complement-dependent pathways. However, the two proteins exploit different mechanisms of complement activation and receptor-mediated phagocytosis, which further extends complexity and integration of the complement-pentraxin crosstalk in the immune response to A. fumigatus. Here we revisit this crosstalk in light of the emerging roles of SAP as a novel PRM with antifungal activity.
Highlights
Aspergillosis is a collective name for Aspergillus species-related infections that clinically manifest as either non-invasive, or invasive diseases [1]
Those who skip mucociliary clearance are promptly recognized, phagocytosed and killed by alveolar epithelial cells and cellular effectors of the innate immune system, including resident alveolar macrophages (AMs) and dendritic cells (DCs) as well as recruited polymorphonuclear neutrophils [5]. These cells are all endowed with an armamentarium of pattern recognition receptors (PRRs) that recognize a spectrum of pathogen associated molecular patterns (PAMPs) on fungal spores, and activate mechanisms of defence [6]
We have recently reported that the classical short pentraxin serum amyloid P component (SAP) promotes recognition, phagocytosis and killing of Aspergillus fumigatus (AF)
Summary
Received: 29 September 2021 Accepted: 01 November 2021 Published: 18 November 2021. Citation: Parente R, Possetti V, Erreni M, D’Autilia F, Bottazzi B, Garlanda C, Mantovani A, Inforzato A and Doni A (2021) Complementary. Recognition of the fungal pathogen, in particular, is mediated by a set of diverse soluble pattern recognition molecules (PRMs) that act as “ancestral antibodies” inasmuch as they are endowed with opsonic, pro-phagocytic and killing properties Pivotal is, in this respect, the contribution of the complement system, which functionally cooperates with cell-borne pattern recognition receptors (PRRs) and other soluble PRMs, including pentraxins. The two proteins exploit different mechanisms of complement activation and receptor-mediated phagocytosis, which further extends complexity and integration of the complementpentraxin crosstalk in the immune response to A. fumigatus. We revisit this crosstalk in light of the emerging roles of SAP as a novel PRM with antifungal activity
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