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

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.

Host, pathogenic fungi and the microbiome: A genetic triangle in infection

“…The interaction between PRRs and PAMPs, leads to the regulation of uptake of fungal pathogens by immune cells. In addition to membrane receptors, soluble PRRs such as pentraxins or mannose binding lectins (MBLs) are also critical for pathogen sensing and efficient phagocytosis ( 18 , 19 ).…”

“…The interaction between PRRs and PAMPs, leads to the regulation of uptake of fungal pathogens by immune cells. In addition to membrane receptors, soluble PRRs such as pentraxins or mannose binding lectins (MBLs) are also critical for pathogen sensing and efficient phagocytosis (18, 19).To date, polymorphisms in PTX3 have been reported in different clinical settings as a risk factor for invasive pulmonary aspergillosis in haematopoietic stem cell transplant recipients (20), solid organ transplants (21) and chronic obstructive pulmonary disease (22). Using ex Frontiers in Immunology frontiersin.org 01…”

Target-Induced AIE Effect Coupled with CRISPR/Cas12a System Dual-Signal Biosensing for the Ultrasensitive Detection of Gliotoxin

“…of different species (human, mouse and fish, etc. ). , In the intervention of GT in mice, it has been found that a higher dose of GT could lead to the death of mice within 12–24 h, and mice that survive more than 12 h develop liver changes of necrotizing and proliferative cholangitis . GT are also determined in the lungs and serum of mice and patients invasive aspergillosis.…”

Humoral Immunity Against Aspergillus fumigatus

“…Short pentraxins include CRP and serum amyloid protein (SAP) while pentraxin-3 (PTX3) is a typical long pentraxin. Their action against A. fumigatus have been recently reviewed [ 69 , 70 ] and is therefore only shortly summarized here. CRP (also known as pentraxin-1) was found to bind A. fumigatus hyphae [ 71 ] and promotes conidial phagocytosis by human neutrophils in vitro [ 72 ] , but its role in fungal pathogenesis remains unknown.…”