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CD4 + T cells mediate antibody-independent acquired immunity to pneumococcal colonization
Open accessAbstract
Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend on the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated whole-cell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD4 + T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD8 + T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD4 + T cells at the time of challenge.
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“Studies show that sterilizing immunity against carriage of S. pneumoniae in mice can be achieved by the transfer of T cells from donor mice exposed to S. pneumoniae40”
From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [40]
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Cites
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Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection
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A guide to vaccinology: from basic principles to new developments
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The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease
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Streptococcus pneumoniae: transmission, colonization and invasion
Weiser, J. N., Ferreira, D. M., & Paton, J. C. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0001-8 · Cited by 1,162
The fundamental link between pneumococcal carriage and disease
Simell, B., Auranen, K. J., Käyhty, H. M., Goldblatt, D., Dagan, R., O’Brien, K. L., & for the Pneumococcal Carriage Group (PneumoCarr) (2012) · Expert Review of Vaccines · doi:10.1586/erv.12.53 · Cited by 633
Interleukin-17A Mediates Acquired Immunity to Pneumococcal Colonization
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Metadata
- Authors
- Malley, R., Trzcinski, K., Srivastava, A., Thompson, C. M., Anderson, P. W., & Lipsitch, M.
- Affiliations
- Boston Children's Hospital (US)
- Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, MA 02115; Departments of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02215; and Department of Pediatrics, University of Rochester, Rochester, NY 14627
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-03-21
- Volume
- 102
- Issue
- 13
- Pages
- 4848-4853
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC555733
- OpenAlex
- W2138424202
- Cited by
- 346
- References
- 35
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 15 · 2017: 27 · 2016: 14 · 2015: 18 · 2014: 23 · 2013: 22 · 2012: 29
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute of Allergy and Infectious Diseases (K08 AI51526-01, K08AI051526, AI07061-26, R01AI048935, T32AI007061)
- Topics
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Streptococcus pneumoniae, pneumococcal carriage, CD4+ T cells, antibody-independent immunity, adaptive immunity, CD8+ T cells, whole-cell vaccine, intranasal immunization, antibody deficiency, T cell-deficient mice, serotype 6B, serotype 7F, serotype 14, mucosal immunity
- MeSH terms
- Administration, Intranasal, Animals, Enzyme-Linked Immunosorbent Assay, Female, Immunity, Cellular, Mice, Inbred C57BL, Pneumococcal Infections, Species Specificity, Streptococcus pneumoniae, Time Factors, CD4-Positive T-Lymphocytes, Streptococcal Vaccines, Mice
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