M-ficolin is present in Aspergillus fumigatus infected lung and modulates epithelial cell immune responses elicited by fungal cell wall polysaccharides

Abstract

View related articles View Crossmark data Citing articles: 12 View citing articles LETTER TO THE EDITOR M-ficolin is present in Aspergillus fumigatus infected lung and modulates epithelial cell immune responses elicited by fungal cell wall polysaccharides

The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

“…In this model, an increased fungal burden was observed in the double-deficient mice compared to WT animals at early times (i.e., 24 h) from infection, consistent with impaired opsonophagocytosis of dormant conidia [67]. Complement activation and recruitment of inflammatory cells were both unaltered in this setting; however, decreased production of proinflammatory cytokines in the lung of ficolin-A-and ficolin-B-deficient mice was reported, which suggests an early immunomodulatory role for these ficolins in vivo, similar to what described in vitro [62].…”

“…As opposed to a-glucans, chitin, the innermost polysaccharide of the fungal cell wall, has been proposed as a ligand of ficolins. In this regard, ficolin-1 recognized chitin (in addition to b-glucans) on the surface of A. fumigatus young hyphae [62], and the binding of ficolins 2 and 3 (and murine ficolin-A) to A. fumigatus conidia was inhibited by N-acetylglucosamine (GlcNAc, the monosaccharide component of chitin), suggesting that they may recognize chitin and exert complement activating functions on germlings and hyphae (in addition to conidia) [67]. The relevance of chitin as a PAMP for complement activation has been recently highlighted in a study on mutant strains of A. fumigatus lacking b-glucans, which synthesized and exposed high levels of chitin (likely through compensatory pathways), and underwent enhanced complement activation and dendritic cell-mediated clearance [68].…”

“…Of these, b-glucans are displayed at high levels on germlings and young hyphae, and masked again (i.e., by the exopolysaccharide GAG) in adult hyphae [60]. In addition to dectin-1 (a well-known PRR for b-glucans that mediates essential innate and adaptive immune responses [37]), ficolin-1 was reported to bind b-glucan-containing, alkali-insoluble hyphal cell wall fractions (AIF) of A. fumigatus [61], in addition to purified b-glucans, and elicit LP activation with enhanced IL-8 secretion by A594 airway epithelial cells in vitro [62].…”

FIBCD1 Binds Aspergillus fumigatus and Regulates Lung Epithelial Response to Cell Wall Components

“…The crystal structure of FIBCD1-FReD ( 16 ) is homologous to FReD superfamily members involved in immune regulation, including ficolin-1 and −2 ( 17 , 18 ). Both ficolin-1 and −2 recognize A. fumigatus -associated PAMPs ( 19 , 20 ) and binds directly or indirectly to resting A. fumigatus conidia ( 21 ).…”

Levels of interleukin (IL)‐6 and IL‐8 are elevated in serum and bronchoalveolar lavage fluid of haematological patients with invasive pulmonary aspergillosis

“…In 1999, Borger and colleagues have reported an up-regulation of gene transcription by Aspergillus fumigatus proteases as cause of increased release of IL-6 and IL-8 by A549 pulmonary epithelial cells and primary epithelial cells 39. More recent studies have shown that in vitro opsonisation of A. fumigatus conidia with H-ficolin,40 L-ficolin23 and M-ficolin,41 which play essential roles in pathogen recognition and complement activation through T A B L E 3 Performance of cytokine levels in serum and bronchoalveolar fluid (BALF) for differentiating cases with probable/proven IPA (n = 10) from matched controls (n = 20)…”