Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms

ABSTRACT Staphylococcus aureus is a major cause of morbidity and mortality worldwide. S. aureus colonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management. S. aureus vaccine development has been unsu...

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Autores principales:	Fan Zhang, Olivia Ledue, Maria Jun, Cibelly Goulart, Richard Malley, Ying-Jie Lu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	B-cell responses Staphylococcus aureus T-cell immunity adaptive immunity vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/07a01a87a63442ea92dae2be88d55921
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spelling	oai:doaj.org-article:07a01a87a63442ea92dae2be88d559212021-11-15T15:58:20ZProtection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms10.1128/mBio.01949-182150-7511https://doaj.org/article/07a01a87a63442ea92dae2be88d559212018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01949-18https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is a major cause of morbidity and mortality worldwide. S. aureus colonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management. S. aureus vaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by an S. aureus vaccine in protection against S. aureus bacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-induced S. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality during S. aureus bacteremia, whereas Th1 or Th17 responses are essential for prevention of S. aureus skin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention of S. aureus dermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses to S. aureus antigens may be critical to achieve effective and comprehensive immune defense against this pathogen. IMPORTANCE S. aureus is a leading cause of healthcare- and community-associated bacterial infections. S. aureus causes various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections. S. aureus colonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development against S. aureus has been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses to S. aureus antigens in conferring enhanced and broad protection against S. aureus invasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.Fan ZhangOlivia LedueMaria JunCibelly GoulartRichard MalleyYing-Jie LuAmerican Society for MicrobiologyarticleB-cell responsesStaphylococcus aureusT-cell immunityadaptive immunityvaccinesMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	B-cell responses Staphylococcus aureus T-cell immunity adaptive immunity vaccines Microbiology QR1-502
spellingShingle	B-cell responses Staphylococcus aureus T-cell immunity adaptive immunity vaccines Microbiology QR1-502 Fan Zhang Olivia Ledue Maria Jun Cibelly Goulart Richard Malley Ying-Jie Lu Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms
description	ABSTRACT Staphylococcus aureus is a major cause of morbidity and mortality worldwide. S. aureus colonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management. S. aureus vaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by an S. aureus vaccine in protection against S. aureus bacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-induced S. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality during S. aureus bacteremia, whereas Th1 or Th17 responses are essential for prevention of S. aureus skin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention of S. aureus dermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses to S. aureus antigens may be critical to achieve effective and comprehensive immune defense against this pathogen. IMPORTANCE S. aureus is a leading cause of healthcare- and community-associated bacterial infections. S. aureus causes various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections. S. aureus colonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development against S. aureus has been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses to S. aureus antigens in conferring enhanced and broad protection against S. aureus invasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.
format	article
author	Fan Zhang Olivia Ledue Maria Jun Cibelly Goulart Richard Malley Ying-Jie Lu
author_facet	Fan Zhang Olivia Ledue Maria Jun Cibelly Goulart Richard Malley Ying-Jie Lu
author_sort	Fan Zhang
title	Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms
title_short	Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms
title_full	Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms
title_fullStr	Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms
title_full_unstemmed	Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms
title_sort	protection against <named-content content-type="genus-species">staphylococcus aureus</named-content> colonization and infection by b- and t-cell-mediated mechanisms
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/07a01a87a63442ea92dae2be88d55921
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Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated Mechanisms

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