Complementary Roles of Short and Long Pentraxins in the Complement-Mediated Immune Response to Aspergillus fumigatus Infections

The ubiquitous mold <i>Aspergillus fumigatus</i> 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 <i>A. fumigatus</i> 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 <i>A. fumigatus</i>, we recently reported that this fungal pathogen is targeted <i>in vitro</i> and <i>in vivo</i> by the short pentraxin Serum Amyloid P component (SAP) too. Similar to PTX3, SAP promotes phagocytosis and disposal of the fungal pathogen <i>via</i> 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 <i>A. fumigatus</i>. Here we revisit this crosstalk in light of the emerging roles of SAP as a novel PRM with antifungal activity.