The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.

Zwitterionic polysaccharide (ZPS) components of the bacterial cell envelope have been shown to exert a major histocompatibility complex (MHC) II-dependent activation of CD4+ T cells, which in turn can modulate the outcome and progression of infections in animal models. We investigated the impact of...

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Autores principales: Christopher Weidenmaier, Rachel M McLoughlin, Jean C Lee
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:715f13f42def481d8af6f4fa74229ef92021-11-18T07:03:34ZThe zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.1932-620310.1371/journal.pone.0013227https://doaj.org/article/715f13f42def481d8af6f4fa74229ef92010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20949105/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Zwitterionic polysaccharide (ZPS) components of the bacterial cell envelope have been shown to exert a major histocompatibility complex (MHC) II-dependent activation of CD4+ T cells, which in turn can modulate the outcome and progression of infections in animal models. We investigated the impact of zwitterionic cell wall teichoic acid (WTA) produced by Staphylococcus aureus on the development of skin abscesses in a mouse model. We also compared the relative biological activities of WTA and capsular polysaccharide (CP), important S. aureus pathogenicity factors, in abscess formation. Expression of both WTA and CP markedly affected the ability of S. aureus to induce skin abscess formation in mice. Purified wild-type zwitterionic WTA was more active in inducing abscess formation than negatively charged mutant WTA or purified CP8. To assess the ability of purified native WTA to stimulate T cell proliferation in vitro, we co-cultivated WTA with human T-cells and antigen presenting cells in the presence and absence of various inhibitors of MHC-II presentation. Wild-type WTA induced T cell proliferation to a significantly greater extent than negatively charged WTA. T cell activation was dependent on the presentation of WTA on MHC II, since inhibitors of MHC II-dependent presentation and antibodies to MHC II significantly reduced T cell proliferation. T cells activated in vitro with wild-type WTA, but not negatively charged WTA, induced abscess formation when injected subcutaneously into wild-type mice. CD4-/- mice similarly injected with WTA failed to develop abscesses. Our results demonstrate that the zwitterionic WTA of S. aureus induces CD4+ T-cell proliferation in an MHCII-dependent manner, which in turn modulates abscess formation in a mouse skin infection model. An understanding of this novel T cell-dependent host response to staphylococcal abscess formation may lead to the development of new strategies to combat S. aureus skin and soft tissue infections.Christopher WeidenmaierRachel M McLoughlinJean C LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13227 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Christopher Weidenmaier
Rachel M McLoughlin
Jean C Lee
The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.
description Zwitterionic polysaccharide (ZPS) components of the bacterial cell envelope have been shown to exert a major histocompatibility complex (MHC) II-dependent activation of CD4+ T cells, which in turn can modulate the outcome and progression of infections in animal models. We investigated the impact of zwitterionic cell wall teichoic acid (WTA) produced by Staphylococcus aureus on the development of skin abscesses in a mouse model. We also compared the relative biological activities of WTA and capsular polysaccharide (CP), important S. aureus pathogenicity factors, in abscess formation. Expression of both WTA and CP markedly affected the ability of S. aureus to induce skin abscess formation in mice. Purified wild-type zwitterionic WTA was more active in inducing abscess formation than negatively charged mutant WTA or purified CP8. To assess the ability of purified native WTA to stimulate T cell proliferation in vitro, we co-cultivated WTA with human T-cells and antigen presenting cells in the presence and absence of various inhibitors of MHC-II presentation. Wild-type WTA induced T cell proliferation to a significantly greater extent than negatively charged WTA. T cell activation was dependent on the presentation of WTA on MHC II, since inhibitors of MHC II-dependent presentation and antibodies to MHC II significantly reduced T cell proliferation. T cells activated in vitro with wild-type WTA, but not negatively charged WTA, induced abscess formation when injected subcutaneously into wild-type mice. CD4-/- mice similarly injected with WTA failed to develop abscesses. Our results demonstrate that the zwitterionic WTA of S. aureus induces CD4+ T-cell proliferation in an MHCII-dependent manner, which in turn modulates abscess formation in a mouse skin infection model. An understanding of this novel T cell-dependent host response to staphylococcal abscess formation may lead to the development of new strategies to combat S. aureus skin and soft tissue infections.
format article
author Christopher Weidenmaier
Rachel M McLoughlin
Jean C Lee
author_facet Christopher Weidenmaier
Rachel M McLoughlin
Jean C Lee
author_sort Christopher Weidenmaier
title The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.
title_short The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.
title_full The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.
title_fullStr The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.
title_full_unstemmed The zwitterionic cell wall teichoic acid of Staphylococcus aureus provokes skin abscesses in mice by a novel CD4+ T-cell-dependent mechanism.
title_sort zwitterionic cell wall teichoic acid of staphylococcus aureus provokes skin abscesses in mice by a novel cd4+ t-cell-dependent mechanism.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/715f13f42def481d8af6f4fa74229ef9
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