Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

Suzan H.M. Rooijakkers; Maartje Ruyken; Anja Roos; Mohamed R. Daha; Julia S. Presanis; Robert B. Sim; Willem J.B. van Wamel; Kok P.M. van Kessel; Jos A.G. van Strijp

doi:10.1038/ni1235

Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

Suzan H.M. Rooijakkers^*
, Maartje Ruyken
, Anja Roos
, Mohamed R. Daha
, Julia S. Presanis
, Robert B. Sim
, Willem J.B. van Wamel
, Kok P.M. van Kessel
, Jos A.G. van Strijp

^*Corresponding author for this work

Utrecht University
Leiden University Medical Centre
University of Oxford
Eijkman Winkler Institute

Research output: Contribution to journal › Article › Academic › peer-review

385 Citations (Scopus)

Abstract

The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.

Original language	English
Pages (from-to)	920-927
Number of pages	8
Journal	Nature Immunology
Volume	6
Issue number	9
DOIs	https://doi.org/10.1038/ni1235
Publication status	Published - Sept 2005
Externally published	Yes

Bibliographical note

Funding Information:
We thank W. Jansen for reviewing the manuscript, and L. de Graaf-Miltenburg for purification of factor B and C3. Supported by the European Union (LSHM-CT-2004-512093 and QLG1-CT-2001-01039).

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title = "Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases",

abstract = "The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.",

author = "Rooijakkers, \{Suzan H.M.\} and Maartje Ruyken and Anja Roos and Daha, \{Mohamed R.\} and Presanis, \{Julia S.\} and Sim, \{Robert B.\} and \{van Wamel\}, \{Willem J.B.\} and \{van Kessel\}, \{Kok P.M.\} and \{van Strijp\}, \{Jos A.G.\}",

note = "Funding Information: We thank W. Jansen for reviewing the manuscript, and L. de Graaf-Miltenburg for purification of factor B and C3. Supported by the European Union (LSHM-CT-2004-512093 and QLG1-CT-2001-01039).",

year = "2005",

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doi = "10.1038/ni1235",

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T1 - Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

AU - Rooijakkers, Suzan H.M.

AU - Ruyken, Maartje

AU - Roos, Anja

AU - Daha, Mohamed R.

AU - Presanis, Julia S.

AU - Sim, Robert B.

AU - van Wamel, Willem J.B.

AU - van Kessel, Kok P.M.

AU - van Strijp, Jos A.G.

N1 - Funding Information: We thank W. Jansen for reviewing the manuscript, and L. de Graaf-Miltenburg for purification of factor B and C3. Supported by the European Union (LSHM-CT-2004-512093 and QLG1-CT-2001-01039).

PY - 2005/9

Y1 - 2005/9

N2 - The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.

AB - The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.

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DO - 10.1038/ni1235

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AN - SCOPUS:24944456390

SN - 1529-2908

VL - 6

SP - 920

EP - 927

JO - Nature Immunology

JF - Nature Immunology

IS - 9

ER -

Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

Abstract

Bibliographical note

UN SDGs

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