MASP-1 and MASP-3 bind directly to aspergillus fumigatus and promote complement activation and phagocytosis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
MASP-1 and MASP-3 bind directly to aspergillus fumigatus and promote complement activation and phagocytosis. / Rosbjerg, Anne; Würzner, Reinhard; Garred, Peter; Skjoedt, Mikkel Ole.
I: Journal of Innate Immunity, Bind 13, Nr. 4, 2021, s. 211-224.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - MASP-1 and MASP-3 bind directly to aspergillus fumigatus and promote complement activation and phagocytosis
AU - Rosbjerg, Anne
AU - Würzner, Reinhard
AU - Garred, Peter
AU - Skjoedt, Mikkel Ole
N1 - Publisher Copyright: © 2021
PY - 2021
Y1 - 2021
N2 - Activation of the complement system is mediated by the interaction between pathogens and pattern recognition molecules (PRMs); mannose-binding lectin (MBL), ficolins, and collectin-10/-11 from the lectin pathway and C1q from the classical pathway. Lectin pathway activation specifically depends on proteases named MBL-associated serine proteases (MASPs) that are found in complexes with PRMs. In this study, we hypothesize that MASPs can recognize selected pathogens independently of PRMs. Using different clinical strains of opportunistic fungi, we have observed that MASPs directly recognize certain fungal pathogens in a way that can facilitate complement activation. Among these were Aspergillus fumigatus - a dangerous pathogen, especially for immunocompromised patients. In flow cytometry and fluorescence microscopy, we found that MASP-1 and -3 bound to all A. fumigatus growth stages (conidia, germ tubes, and hyphae), whereas rMASP-2 and the nonproteolytic rMAP-1 did not. Bound rMASPs could recruit rMBL and rficolin-3 to A. fumigatus conidia in a nonclassical manner and activate complement via rMASP-2. In experiments using recombinant and purified components, rMASP-1 increased the neutrophilic phagocytosis of conidia. In serum where known complement activation pathways were blocked, phagocytosis could be mediated by rMASP-3. We have encountered an unknown pathway for complement activation and found that MASP-1 and MASP-3 have dual functions as enzymes and as PRMs.
AB - Activation of the complement system is mediated by the interaction between pathogens and pattern recognition molecules (PRMs); mannose-binding lectin (MBL), ficolins, and collectin-10/-11 from the lectin pathway and C1q from the classical pathway. Lectin pathway activation specifically depends on proteases named MBL-associated serine proteases (MASPs) that are found in complexes with PRMs. In this study, we hypothesize that MASPs can recognize selected pathogens independently of PRMs. Using different clinical strains of opportunistic fungi, we have observed that MASPs directly recognize certain fungal pathogens in a way that can facilitate complement activation. Among these were Aspergillus fumigatus - a dangerous pathogen, especially for immunocompromised patients. In flow cytometry and fluorescence microscopy, we found that MASP-1 and -3 bound to all A. fumigatus growth stages (conidia, germ tubes, and hyphae), whereas rMASP-2 and the nonproteolytic rMAP-1 did not. Bound rMASPs could recruit rMBL and rficolin-3 to A. fumigatus conidia in a nonclassical manner and activate complement via rMASP-2. In experiments using recombinant and purified components, rMASP-1 increased the neutrophilic phagocytosis of conidia. In serum where known complement activation pathways were blocked, phagocytosis could be mediated by rMASP-3. We have encountered an unknown pathway for complement activation and found that MASP-1 and MASP-3 have dual functions as enzymes and as PRMs.
KW - Aspergillosis
KW - Fungi
KW - Lectin pathway
KW - Mannose-binding lectin-associated serine protease
KW - Pattern recognition molecules
U2 - 10.1159/000514546
DO - 10.1159/000514546
M3 - Journal article
C2 - 33780946
AN - SCOPUS:85103601993
VL - 13
SP - 211
EP - 224
JO - Journal of Innate Immunity
JF - Journal of Innate Immunity
SN - 1662-811X
IS - 4
ER -
ID: 301343234