Interplay between host humoral pattern recognition molecules controls undue immune responses against Aspergillus fumigatus

Sarah Dellière, Camille Chauvin, Sarah Sze Wah Wong, Markus Gressler, Valentina Possetti, Raffaella Parente, Thierry Fontaine, Thomas Krüger, Olaf Kniemeyer, Jagadeesh Bayry, Agostinho Carvalho, Axel A. Brakhage, Antonio Inforzato, Jean-Paul Latgé and Vishukumar Aimanianda ()
Additional contact information
Sarah Dellière: Unité Mycologie Moléculaire
Camille Chauvin: Université de Paris-Cité
Sarah Sze Wah Wong: Unité Mycologie Moléculaire
Markus Gressler: Unité des Aspergillus
Valentina Possetti: Pieve Emanuele
Raffaella Parente: IRCCS Humanitas Research Hospital
Thierry Fontaine: Unité des Aspergillus
Thomas Krüger: and Infection Biology (Leibniz-HKI)
Olaf Kniemeyer: and Infection Biology (Leibniz-HKI)
Jagadeesh Bayry: Université de Paris-Cité
Agostinho Carvalho: University of Minho
Axel A. Brakhage: and Infection Biology (Leibniz-HKI)
Antonio Inforzato: Pieve Emanuele
Jean-Paul Latgé: Unité des Aspergillus
Vishukumar Aimanianda: Unité Mycologie Moléculaire

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Pentraxin 3 (PTX3), a long pentraxin and a humoral pattern recognition molecule (PRM), has been demonstrated to be protective against Aspergillus fumigatus, an airborne human fungal pathogen. We explored its mode of interaction with A. fumigatus, and the resulting implications in the host immune response. Here, we demonstrate that PTX3 interacts with A. fumigatus in a morphotype-dependent manner: (a) it recognizes germinating conidia through galactosaminogalactan, a surface exposed cell wall polysaccharide of A. fumigatus, (b) in dormant conidia, surface proteins serve as weak PTX3 ligands, and (c) surfactant protein D (SP-D) and the complement proteins C1q and C3b, the other humoral PRMs, enhance the interaction of PTX3 with dormant conidia. SP-D, C3b or C1q opsonized conidia stimulated human primary immune cells to release pro-inflammatory cytokines and chemokines. However, subsequent binding of PTX3 to SP-D, C1q or C3b opsonized conidia significantly decreased the production of pro-inflammatory cytokines/chemokines. PTX3 opsonized germinating conidia also significantly lowered the production of pro-inflammatory cytokines/chemokines while increasing IL-10 (an anti-inflammatory cytokine) released by immune cells when compared to the unopsonized counterpart. Overall, our study demonstrates that PTX3 recognizes A. fumigatus either directly or by interplaying with other humoral PRMs, thereby restraining detrimental inflammation. Moreover, PTX3 levels were significantly higher in the serum of patients with invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA), supporting previous observations in IPA patients, and suggesting that it could be a potential panel-biomarker for these pathological conditions caused by A. fumigatus.

Date: 2024
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DOI: 10.1038/s41467-024-51047-9

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