Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT Heritable defects in human B cell/antibody development are not associated with increased susceptibility to Staphylococcus aureus infection. Protein A (SpA), a surface molecule of S. aureus, binds the Fcγ domain of immunoglobulin (Ig) and cross-links the Fab domain of VH3-type B cell recepto...

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Autores principales:	Fabiana Falugi, Hwan Keun Kim, Dominique M. Missiakas, Olaf Schneewind
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a05a2e6c0daa423e9e37419b41925bee
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spelling	oai:doaj.org-article:a05a2e6c0daa423e9e37419b41925bee2021-11-15T15:42:47ZRole of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mBio.00575-132150-7511https://doaj.org/article/a05a2e6c0daa423e9e37419b41925bee2013-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00575-13https://doaj.org/toc/2150-7511ABSTRACT Heritable defects in human B cell/antibody development are not associated with increased susceptibility to Staphylococcus aureus infection. Protein A (SpA), a surface molecule of S. aureus, binds the Fcγ domain of immunoglobulin (Ig) and cross-links the Fab domain of VH3-type B cell receptors (IgM). Here we generated S. aureus spa variants harboring amino acid substitutions at four key residues in each of the five Ig-binding domains of SpA. Wild-type S. aureus required SpA binding to Ig to resist phagocytosis and SpA-mediated B cell receptor cross-linking to block antibody development in mice. The spaKKAA mutant, which cannot bind Ig or IgM, was phagocytosed and elicited B cell responses to key virulence antigens that protected animals against lethal S. aureus challenge. The immune evasive attributes of S. aureus SpA were abolished in µMT mice lacking mature B cells and antibodies. Thus, while wild-type S. aureus escapes host immune surveillance, the spaKKAA variant elicits adaptive responses that protect against recurrent infection. IMPORTANCE Staphylococcus aureus causes recurrent skin and bloodstream infections without eliciting immunity. Heritable defects in neutrophil and T cell function, but not B cell or antibody development, are associated with increased incidence of S. aureus infection, and efforts to develop antibody-based S. aureus vaccines have thus far been unsuccessful. We show here that the Fcγ and VH3-type Fab binding activities of staphylococcal protein A (SpA) are essential for S. aureus escape from host immune surveillance in mice. The virulence attributes of SpA in mice required mature B cells and immunoglobulin. These results suggest that antibodies and B cells play a key role in the pathogenesis of staphylococcal infections and provide insights into the development of a vaccine against S. aureus.Fabiana FalugiHwan Keun KimDominique M. MissiakasOlaf SchneewindAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 5 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Fabiana Falugi Hwan Keun Kim Dominique M. Missiakas Olaf Schneewind Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT Heritable defects in human B cell/antibody development are not associated with increased susceptibility to Staphylococcus aureus infection. Protein A (SpA), a surface molecule of S. aureus, binds the Fcγ domain of immunoglobulin (Ig) and cross-links the Fab domain of VH3-type B cell receptors (IgM). Here we generated S. aureus spa variants harboring amino acid substitutions at four key residues in each of the five Ig-binding domains of SpA. Wild-type S. aureus required SpA binding to Ig to resist phagocytosis and SpA-mediated B cell receptor cross-linking to block antibody development in mice. The spaKKAA mutant, which cannot bind Ig or IgM, was phagocytosed and elicited B cell responses to key virulence antigens that protected animals against lethal S. aureus challenge. The immune evasive attributes of S. aureus SpA were abolished in µMT mice lacking mature B cells and antibodies. Thus, while wild-type S. aureus escapes host immune surveillance, the spaKKAA variant elicits adaptive responses that protect against recurrent infection. IMPORTANCE Staphylococcus aureus causes recurrent skin and bloodstream infections without eliciting immunity. Heritable defects in neutrophil and T cell function, but not B cell or antibody development, are associated with increased incidence of S. aureus infection, and efforts to develop antibody-based S. aureus vaccines have thus far been unsuccessful. We show here that the Fcγ and VH3-type Fab binding activities of staphylococcal protein A (SpA) are essential for S. aureus escape from host immune surveillance in mice. The virulence attributes of SpA in mice required mature B cells and immunoglobulin. These results suggest that antibodies and B cells play a key role in the pathogenesis of staphylococcal infections and provide insights into the development of a vaccine against S. aureus.
format	article
author	Fabiana Falugi Hwan Keun Kim Dominique M. Missiakas Olaf Schneewind
author_facet	Fabiana Falugi Hwan Keun Kim Dominique M. Missiakas Olaf Schneewind
author_sort	Fabiana Falugi
title	Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	role of protein a in the evasion of host adaptive immune responses by <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/a05a2e6c0daa423e9e37419b41925bee
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Role of Protein A in the Evasion of Host Adaptive Immune Responses by <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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