Afficher la couverture 'Interplay between host humoral pattern recognition molecules controls undue immune responses against Aspergillus fumigatus | Dellière, Sarah' en grand format
/5

0 avis

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

Archive ouverte

Dellière, Sarah | Chauvin, Camille | Wong, Sarah Sze Wah | Gressler, Markus | Possetti, Valentina | Parente, Raffaella | Fontaine, Thierry | Krüger, Thomas | Kniemeyer, Olaf | Bayry, Jagadeesh | Carvalho, Agostinho | Brakhage, Axel | Inforzato, Antonio | Latgé, Jean-Paul | Aimanianda, Vishukumar

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

Suggestions

Du même auteur

The Role of RodA-Conserved Cysteine Residues in the Aspergillus fumigatus Conidial Surface Organization

Archive ouverte | Valsecchi, Isabel | CCSD

International audience. Immune inertness of Aspergillusfumigatus conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. E...

Members of protein O-mannosyltransferase family in Aspergillus fumigatus differentially affect growth, morphogenesis and viability.

Archive ouverte | Mouyna, Isabelle | CCSD

International audience. O-mannosylation is an essential protein modification in eukaryotes. It is initiated at the endoplasmic reticulum by O-mannosyltransferases (PMT) that are evolutionary conserved from yeast to ...

Surface Structure Characterization of Aspergillus fumigatus Conidia Mutated in the Melanin Synthesis Pathway and Their Human Cellular Immune Response. Surface Structure Characterization of Aspergillus fumigatus Conidia Mutated in the Melanin Synthesis Pathway and Their Human Cellular Immune Response: Melanin mutants of Aspergillus fumigatus and immune response

Archive ouverte | Bayry, Jagadeesh | CCSD

International audience. In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin b...

Chargement des enrichissements...