Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid

Emilie Vassal-Stermann; Monique Lacroix; Evelyne Gout; Emmanuelle Laffly; Christian Marcus Pedersen; Lydie Martin; Ana Amoroso; Richard R. Schmidt; Ulrich Zähringer; Christine Gaboriaud; Anne Marie Di Guilmi; Nicole M. Thielens

doi:10.4049/jimmunol.1400127

Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid

Emilie Vassal-Stermann, Monique Lacroix, Evelyne Gout, Emmanuelle Laffly, Christian Marcus Pedersen, Lydie Martin, Ana Amoroso, Richard R. Schmidt, Ulrich Zähringer, Christine Gaboriaud, Anne Marie Di Guilmi, Nicole M. Thielens^*

^*Corresponding author af dette arbejde

Kemisk Institut

19 Citationer (Scopus)

Abstract

Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal clinical isolates, but its ligands and especially its molecular specificity remain to be identified. Using solid-phase binding assays, serum and recombinant L-ficolins were shown to interact with serotype 2 pneumococcal strain D39 and its unencapsulated R6 derivative. Incubation of both strains with serum triggered complement activation, as measured by C4b and C3b deposition, which was decreased by using ficolin-depleted serum. Recombinant L-ficolin and its FBG-like recognition domain bound to isolated pneumococcal cell wall extracts, whereas binding to cell walls depleted of teichoic acid (TA) was decreased. Both proteins were also shown to interact with two synthetic TA compounds, each comprising part structures of the complete lipoteichoic acid molecule with two PCho residues. Competition studies and direct interaction measurements by surface plasmon resonance identified PCho as a novel L-ficolin ligand. Structural analysis of complexes of the FBG domain of L-ficolin and PCho revealed that the phosphate moiety interacts with amino acids previously shown to define an acetyl binding site. Consequently, binding of L-ficolin to immobilized acetylated BSA was inhibited by PCho and synthetic TA. Binding of serum L-ficolin to immobilized synthetic TA and PCho-conjugated BSA triggered activation of the lectin complement pathway, thus further supporting the hypothesis of L-ficolin involvement in host antipneumococcal defense.

Originalsprog	Engelsk
Tidsskrift	Journal of Immunology
Vol/bind	193
Udgave nummer	11
Sider (fra-til)	5699-5708
Antal sider	10
ISSN	0022-1767
DOI	https://doi.org/10.4049/jimmunol.1400127
Status	Udgivet - 2014

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10.4049/jimmunol.1400127

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title = "Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid",

abstract = "Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal clinical isolates, but its ligands and especially its molecular specificity remain to be identified. Using solid-phase binding assays, serum and recombinant L-ficolins were shown to interact with serotype 2 pneumococcal strain D39 and its unencapsulated R6 derivative. Incubation of both strains with serum triggered complement activation, as measured by C4b and C3b deposition, which was decreased by using ficolin-depleted serum. Recombinant L-ficolin and its FBG-like recognition domain bound to isolated pneumococcal cell wall extracts, whereas binding to cell walls depleted of teichoic acid (TA) was decreased. Both proteins were also shown to interact with two synthetic TA compounds, each comprising part structures of the complete lipoteichoic acid molecule with two PCho residues. Competition studies and direct interaction measurements by surface plasmon resonance identified PCho as a novel L-ficolin ligand. Structural analysis of complexes of the FBG domain of L-ficolin and PCho revealed that the phosphate moiety interacts with amino acids previously shown to define an acetyl binding site. Consequently, binding of L-ficolin to immobilized acetylated BSA was inhibited by PCho and synthetic TA. Binding of serum L-ficolin to immobilized synthetic TA and PCho-conjugated BSA triggered activation of the lectin complement pathway, thus further supporting the hypothesis of L-ficolin involvement in host antipneumococcal defense.",

author = "Emilie Vassal-Stermann and Monique Lacroix and Evelyne Gout and Emmanuelle Laffly and Pedersen, {Christian Marcus} and Lydie Martin and Ana Amoroso and Schmidt, {Richard R.} and Ulrich Z{\"a}hringer and Christine Gaboriaud and Guilmi, {Anne Marie Di} and Thielens, {Nicole M.}",

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doi = "10.4049/jimmunol.1400127",

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T1 - Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid

AU - Vassal-Stermann, Emilie

AU - Lacroix, Monique

AU - Gout, Evelyne

AU - Laffly, Emmanuelle

AU - Pedersen, Christian Marcus

AU - Martin, Lydie

AU - Amoroso, Ana

AU - Schmidt, Richard R.

AU - Zähringer, Ulrich

AU - Gaboriaud, Christine

AU - Guilmi, Anne Marie Di

AU - Thielens, Nicole M.

PY - 2014

Y1 - 2014

N2 - Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal clinical isolates, but its ligands and especially its molecular specificity remain to be identified. Using solid-phase binding assays, serum and recombinant L-ficolins were shown to interact with serotype 2 pneumococcal strain D39 and its unencapsulated R6 derivative. Incubation of both strains with serum triggered complement activation, as measured by C4b and C3b deposition, which was decreased by using ficolin-depleted serum. Recombinant L-ficolin and its FBG-like recognition domain bound to isolated pneumococcal cell wall extracts, whereas binding to cell walls depleted of teichoic acid (TA) was decreased. Both proteins were also shown to interact with two synthetic TA compounds, each comprising part structures of the complete lipoteichoic acid molecule with two PCho residues. Competition studies and direct interaction measurements by surface plasmon resonance identified PCho as a novel L-ficolin ligand. Structural analysis of complexes of the FBG domain of L-ficolin and PCho revealed that the phosphate moiety interacts with amino acids previously shown to define an acetyl binding site. Consequently, binding of L-ficolin to immobilized acetylated BSA was inhibited by PCho and synthetic TA. Binding of serum L-ficolin to immobilized synthetic TA and PCho-conjugated BSA triggered activation of the lectin complement pathway, thus further supporting the hypothesis of L-ficolin involvement in host antipneumococcal defense.

AB - Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal clinical isolates, but its ligands and especially its molecular specificity remain to be identified. Using solid-phase binding assays, serum and recombinant L-ficolins were shown to interact with serotype 2 pneumococcal strain D39 and its unencapsulated R6 derivative. Incubation of both strains with serum triggered complement activation, as measured by C4b and C3b deposition, which was decreased by using ficolin-depleted serum. Recombinant L-ficolin and its FBG-like recognition domain bound to isolated pneumococcal cell wall extracts, whereas binding to cell walls depleted of teichoic acid (TA) was decreased. Both proteins were also shown to interact with two synthetic TA compounds, each comprising part structures of the complete lipoteichoic acid molecule with two PCho residues. Competition studies and direct interaction measurements by surface plasmon resonance identified PCho as a novel L-ficolin ligand. Structural analysis of complexes of the FBG domain of L-ficolin and PCho revealed that the phosphate moiety interacts with amino acids previously shown to define an acetyl binding site. Consequently, binding of L-ficolin to immobilized acetylated BSA was inhibited by PCho and synthetic TA. Binding of serum L-ficolin to immobilized synthetic TA and PCho-conjugated BSA triggered activation of the lectin complement pathway, thus further supporting the hypothesis of L-ficolin involvement in host antipneumococcal defense.

U2 - 10.4049/jimmunol.1400127

DO - 10.4049/jimmunol.1400127

M3 - Journal article

C2 - 25344472

AN - SCOPUS:84912573300

SN - 0022-1767

VL - 193

SP - 5699

EP - 5708

JO - Journal of Immunology

JF - Journal of Immunology

IS - 11

ER -

Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid

Abstract

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