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Protection acquired upon intraperitoneal group a Streptococcus immunization is independent of concurrent adaptive immune responses but relies on macrophages and IFN-γ

Emami, Shiva LU ; Westerlund, Elsa LU ; Rojas Converso, Thiago LU ; Johansson-Lindbom, Bengt LU and Persson, Jenny J. LU (2025) In Virulence 16(1).
Abstract

Group A Streptococcus (GAS; Streptococcus pyogenes) is an important bacterial pathogen causing over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >250 distinct emm (M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyse the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and... (More)

Group A Streptococcus (GAS; Streptococcus pyogenes) is an important bacterial pathogen causing over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >250 distinct emm (M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyse the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells and is accompanied by the induction of an altered acute cytokine profile upon subsequent infection, noticeable e.g. by the absence of classical pro-inflammatory cytokines and increased IFN-γ production. Further, the ability of immunized mice to survive a lethal infection is dependent on macrophages and the macrophage-activating cytokine IFN-γ. To our knowledge these findings are the first to suggest that GAS may have the ability to induce forms of trained innate immunity. Taken together, the current study proposes a novel role for the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adaptive immune memory, Group A Streptococcus, immunization, innate immune memory, protective immunity
in
Virulence
volume
16
issue
1
article number
2457957
publisher
Landes Bioscience
external identifiers
  • pmid:39921669
  • scopus:85217158397
ISSN
2150-5594
DOI
10.1080/21505594.2025.2457957
language
English
LU publication?
yes
id
8da4111b-9d3f-4c3a-b475-164f7013b9b2
date added to LUP
2025-04-09 11:24:53
date last changed
2025-07-16 19:13:51
@article{8da4111b-9d3f-4c3a-b475-164f7013b9b2,
  abstract     = {{<p>Group A Streptococcus (GAS; Streptococcus pyogenes) is an important bacterial pathogen causing over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into &gt;250 distinct emm (M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyse the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells and is accompanied by the induction of an altered acute cytokine profile upon subsequent infection, noticeable e.g. by the absence of classical pro-inflammatory cytokines and increased IFN-γ production. Further, the ability of immunized mice to survive a lethal infection is dependent on macrophages and the macrophage-activating cytokine IFN-γ. To our knowledge these findings are the first to suggest that GAS may have the ability to induce forms of trained innate immunity. Taken together, the current study proposes a novel role for the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines.</p>}},
  author       = {{Emami, Shiva and Westerlund, Elsa and Rojas Converso, Thiago and Johansson-Lindbom, Bengt and Persson, Jenny J.}},
  issn         = {{2150-5594}},
  keywords     = {{adaptive immune memory; Group A Streptococcus; immunization; innate immune memory; protective immunity}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Landes Bioscience}},
  series       = {{Virulence}},
  title        = {{Protection acquired upon intraperitoneal group a Streptococcus immunization is independent of concurrent adaptive immune responses but relies on macrophages and IFN-γ}},
  url          = {{http://dx.doi.org/10.1080/21505594.2025.2457957}},
  doi          = {{10.1080/21505594.2025.2457957}},
  volume       = {{16}},
  year         = {{2025}},
}