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. 2017 Nov 17;8(8):1870-1879.
doi: 10.1080/21505594.2016.1278337. Epub 2017 Feb 16.

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

Kasper Jensen  1 , Kit P Lund  1 , Kimmie B Christensen  1 , Anne T Holm  1 , Lalit Kumar Dubey  1   2 , Jesper B Moeller  1   3 , Christine S Jepsen  1 , Anders Schlosser  1 , László Galgóczy  4   5 , Steffen Thiel  6 , Uffe Holmskov  1 , Grith L Sorensen  1
Affiliations

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

Kasper Jensen et al. Virulence. .
No abstract available

Keywords: Aspergillus fumigatus; M-ficolin; chitin; complement; interleukin-8; β-1,3-glucan.

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Figures

Figure 1.
Figure 1.
Immunohistochemical localization of M-ficolin to the aspergilloma. Brown staining indicates presence of M-ficolin. (A) Control immunostaining of monocytes/granulocytes in the spleen. (B) Control alveolar tissue. Overview of elongated A. fumigatus fungal balls surrounded by pulmonary scar tissue in patient 1 (C) and patient 2 (D). The boxes indicate the location of images E-G. (E) Pulmonary scar tissue and A. fumigatus mycelial zone. (F-G) Peripheral zone of aspergilloma (Upper insert: granulocyte. Lower insert: monocyte). (H) Pulmonary blood vessels in scar tissue from a lung with A. fumigatus infection. Fo = follicle. A = A. fumigatus. Scar = scar tissue. The lengths of the bars are in micrometers.
Figure 2.
Figure 2.
Characterization of M-ficolin binding to A. fumigatus. The binding between M-ficolin and A. fumigatus strains NRRL 174 (174), SZMC 2419 (2419), SZMC 2421 (2421), SZMC 2422 (2422) and SZMC 2430 (2430) was on conidia (0 hours) and germlings (8 hours) using pull-down assays in the presence of (A) 5 mM Ca2+ or (B) 10 mM EDTA. The data are triplicates from 2 independently performed experiments. Data shown are mean ± SEM. Significance was determined using 2-way ANOVA with Holm-Sidak's multiple comparison test, *p < 0.05, **p < 0.01, ****p < 0.001. (C) Light microscopy of growing hyphae, original magnification 100×. (D) Light microscopy of growing hyphae, original magnification 400×. (E-F) Localization of regions recognized by M-ficolin (green) and (G-H) localization of chitin (WGA, red). (I-J) Overlay images. The lengths of the bars are in micrometers.
Figure 3.
Figure 3.
Pull-down assays with rM-ficolin binding the polysaccharides chitin, β-glucan and A. fumigatus AIF. Western blotting assays using the monoclonal anti-M-ficolin 7G1 antibody to detect rM-ficolin in the pellet resulting from incubation with (A) chitin beads, (B) β-1,3 glucan, (C) A. fumigatus AIF and (D) acHSA beads (control). The binding was performed in the presence of 10 mM EDTA, 50 mM acetate, propionate, glucose, glucosamine, or GlcNAc. The results are representative of 3 independent experiments. rM-ficolin was further measured by ELISA in the supernatant resulting from incubation with (E) chitin, (F) β-1,3 glucan and (G) A. fumigatus AIF and (H) acHSA beads. The data are from 3 independent experiments. The data shown are mean ± SEM. The data were analyzed by one-way ANOVA with Holm-Sidak's multiple comparisons test, *p < 0.05, **p < 0.01, ***p < 0.001.
Figure 4.
Figure 4.
Functional interactions between rM-ficolin and fungal polysaccharides. (A) Concentration-dependent rM-ficolin-mediated chitin complement C4 consumption assay and complement C4b generation assays for (B) β-1,3 glucan, (C) A. fumigatus AIF and (D) acHSA (control). Dry weight (mg) of A. fumigatus (E) NRRL 174 and (F) SZMC 2430 cultures before and after an 8-hours incubation in 50% MBL-deficient serum and in the presence of various concentrations (0–1500 ng/ml) of rM-ficolin. (G) IL-8 secretion in A549 cell CS collected 6 hours after challenge with rM-ficolin alone or after incubation with A. fumigatus AIF or increasing concentrations of rM-ficolin opsonized A. fumigatus AIF. Blank control = serum free medium. The data shown are mean ± SEM of quadruplicate measurements representative of 2 (A) and duplicates from 3 (B-G) independent experiments, *p < 0.5, ##, $$p < 0.01, ***, $$$p < 0.001. *relative to background, #relative to A. fumigatus AIF control, $relative to rM-ficolin control.
Figure 5.
Figure 5.
Schematic depiction of the interaction between M-ficolin-opsonized A. fumigatus and the innate immune system of the host. M-ficolin interacts with different life stages of A. fumigatus. The M-ficolin ligand on the surface of resting conidia (1) is unknown, however the effects of opsonization may be overlapping with other A. fumigatus life stages. Swollen conidia (2), germlings (3) and hyphae forming stages (4) expose cell wall polysaccharides β-glucan and chitin, which mediates M-ficolin interaction. M-ficolin enhances fungal polysaccharide-mediated pulmonary epithelial IL-8 secretion involved in phagocyte recruitment and enhances complement activation. The complement activation does not result in the formation of membrane attack complexes (MAC). Possible effects of M-ficolin-enhanced activation of phagocyte functions are unknown.
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References

    1. Gersuk GM, Underhill DM, Zhu L, Marr KA. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J Immunol 2006; 176:3717-24; PMID:16517740; https://doi.org/10.4049/jimmunol.176.6.3717 - DOI - PubMed
    1. Thomsen T, Moeller JB, Schlosser A, Sorensen GL, Moestrup SK, Palaniyar N, Wallis R, Mollenhauer J, Holmskov U. The recognition unit of FIBCD1 organizes into a noncovalently linked tetrameric structure and uses a hydrophobic funnel (S1) for acetyl group recognition. J Biol Chem 2010; 285:1229-38; PMID:19892701; https://doi.org/10.1074/jbc.M109.061523 - DOI - PMC - PubMed
    1. Becker KL, Aimanianda V, Wang X, Gresnigt MS, Ammerdorffer A, Jacobs CW, Gazendam RP, Joosten LA, Netea MG, Latgé JP, et al.. Aspergillus Cell Wall Chitin Induces Anti- and Proinflammatory Cytokines in Human PBMCs via the Fc-γ Receptor/Syk/PI3K Pathway. MBio 2016; 7:e01823-15; PMID:27247234; https://doi.org/10.1128/mBio.01823-15 - DOI - PMC - PubMed
    1. Thomsen T, Schlosser A, Holmskov U, Sorensen GL. Ficolins and FIBCD1: soluble and membrane bound pattern recognition molecules with acetyl group selectivity. Mol Immunol 2011; 48:369-81; PMID:21071088; https://doi.org/10.1016/j.molimm.2010.09.019 - DOI - PubMed
    1. Genster N, Praestekjaer Cramer E, Rosbjerg A, Pilely K, Cowland JB, Garred P. Ficolins promote fungal clearance in vivo and modulate the inflammatory cytokine response in host defense against aspergillus fumigatus. J Innate Immun 2016; 8(6):579-588; PMID:27467404; https://doi.org/10.1159/000447714 - DOI - PMC - PubMed

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