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Insertion of an imm...
Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-γ-dependent shift from a non-protective to a protective immune response
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- Emami, Shiva (författare)
- Lund University,Lunds universitet,Adaptivt immunförsvar,Forskargrupper vid Lunds universitet,Adaptive Immunity,Lund University Research Groups
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- Rojas Converso, Thiago (författare)
- Lund University,Lunds universitet,Experimentell infektionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Experimental Infection Medicine, Malmö,Lund University Research Groups
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- Persson, Jenny J. (författare)
- Lund University,Lunds universitet,Värd-patogeninteraktioner,Forskargrupper vid Lunds universitet,Host-Pathogen Interactions,Lund University Research Groups
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- Johansson-Lindbom, Bengt (författare)
- Lund University,Lunds universitet,Adaptivt immunförsvar,Forskargrupper vid Lunds universitet,Adaptive Immunity,Lund University Research Groups
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- The common pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) is an extracellular bacterium that is associated with a multitude of infectious syndromes spanning a wide range of severity. The surface-exposed M protein is a major GAS virulence factor that is also target for protective antibody responses. In this study, we use a murine immunization model to investigate aspects of the cellular and molecular foundation for protective adaptive immune responses generated against GAS. We show that a wild type M1 GAS strain induces a non-protective antibody response, while an isogenic strain carrying the immunodominant 2W T helper cell epitope within the M protein elicits an immune response that is protective against the parental non-recombinant M1 GAS strain. Although the two strains induce total anti-GAS IgG levels of similar magnitude, only the 2W-carrying strain promotes elevated titers of the complement-fixing IgG2c subclass. Protection is dependent on IFN-γ, and IFN-γ-deficient mice show a specific reduction in IgG2c levels. Our findings suggest that inclusion of the 2W T cell epitope in the M protein confers essential qualitative alterations in the adaptive immune response against GAS, and that sparsity in IFN-γ-promoting Th cell epitopes in the M protein may constitute an immune evasion mechanism, evolved to allow the pathogen to avoid attack by complement-fixing antibodies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Antibodies
- B cells
- group A Streptococcus
- IFN-γ
- IgG2c
- M protein
- protection
- T cells
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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