Cargando…
Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs
Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V(H)3 clan B cell receptors (IgM), is the staphylococcal determinant for host im...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313907/ https://www.ncbi.nlm.nih.gov/pubmed/25564466 http://dx.doi.org/10.1128/mBio.02369-14 |
_version_ | 1782355277248462848 |
---|---|
author | Kim, Hwan Keun Falugi, Fabiana Thomer, Lena Missiakas, Dominique M. Schneewind, Olaf |
author_facet | Kim, Hwan Keun Falugi, Fabiana Thomer, Lena Missiakas, Dominique M. Schneewind, Olaf |
author_sort | Kim, Hwan Keun |
collection | PubMed |
description | Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V(H)3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High V(H)3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpA(KKAA), which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. Importance Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines. |
format | Online Article Text |
id | pubmed-4313907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-43139072015-02-02 Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs Kim, Hwan Keun Falugi, Fabiana Thomer, Lena Missiakas, Dominique M. Schneewind, Olaf mBio Research Article Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V(H)3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High V(H)3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpA(KKAA), which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. Importance Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines. American Society of Microbiology 2015-01-06 /pmc/articles/PMC4313907/ /pubmed/25564466 http://dx.doi.org/10.1128/mBio.02369-14 Text en Copyright © 2015 Kim et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kim, Hwan Keun Falugi, Fabiana Thomer, Lena Missiakas, Dominique M. Schneewind, Olaf Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs |
title | Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs |
title_full | Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs |
title_fullStr | Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs |
title_full_unstemmed | Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs |
title_short | Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs |
title_sort | protein a suppresses immune responses during staphylococcus aureus bloodstream infection in guinea pigs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313907/ https://www.ncbi.nlm.nih.gov/pubmed/25564466 http://dx.doi.org/10.1128/mBio.02369-14 |
work_keys_str_mv | AT kimhwankeun proteinasuppressesimmuneresponsesduringstaphylococcusaureusbloodstreaminfectioninguineapigs AT falugifabiana proteinasuppressesimmuneresponsesduringstaphylococcusaureusbloodstreaminfectioninguineapigs AT thomerlena proteinasuppressesimmuneresponsesduringstaphylococcusaureusbloodstreaminfectioninguineapigs AT missiakasdominiquem proteinasuppressesimmuneresponsesduringstaphylococcusaureusbloodstreaminfectioninguineapigs AT schneewindolaf proteinasuppressesimmuneresponsesduringstaphylococcusaureusbloodstreaminfectioninguineapigs |