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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2018-11-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01949-18 |
| _version_ | 1818844387943120896 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T05:12:58Z |
| format | Article |
| id | doaj.art-07a01a87a63442ea92dae2be88d55921 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T05:12:58Z |
| publishDate | 2018-11-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-07a01a87a63442ea92dae2be88d559212022-12-21T20:34:45ZengAmerican Society for MicrobiologymBio2150-75112018-11-019510.1128/mBio.01949-18Protection against <named-content content-type="genus-species">Staphylococcus aureus</named-content> Colonization and Infection by B- and T-Cell-Mediated MechanismsFan Zhang0Olivia Ledue1Maria Jun2Cibelly Goulart3Richard Malley4Ying-Jie Lu5Department of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USACentro de Biotecnologia, Instituto Butantan, São Paulo, BrazilDepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Medicine, Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.01949-18B-cell responsesStaphylococcus aureusT-cell immunityadaptive immunityvaccines |
| spellingShingle | 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 mBio B-cell responses Staphylococcus aureus T-cell immunity adaptive immunity vaccines |
| title | 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_short | 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 |
| topic | B-cell responses Staphylococcus aureus T-cell immunity adaptive immunity vaccines |
| url | https://journals.asm.org/doi/10.1128/mBio.01949-18 |
| work_keys_str_mv | AT fanzhang protectionagainstnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcolonizationandinfectionbybandtcellmediatedmechanisms AT olivialedue protectionagainstnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcolonizationandinfectionbybandtcellmediatedmechanisms AT mariajun protectionagainstnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcolonizationandinfectionbybandtcellmediatedmechanisms AT cibellygoulart protectionagainstnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcolonizationandinfectionbybandtcellmediatedmechanisms AT richardmalley protectionagainstnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcolonizationandinfectionbybandtcellmediatedmechanisms AT yingjielu protectionagainstnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentcolonizationandinfectionbybandtcellmediatedmechanisms |