Antibodies to the conserved region of the M protein and a streptococcal superantigen cooperatively resolve toxic shock-like syndrome in HLA-humanized mice.
Animals
Antibodies, Bacterial
/ immunology
Antigens, Bacterial
/ immunology
Bacterial Outer Membrane Proteins
/ immunology
Bacterial Proteins
/ immunology
Carrier Proteins
/ immunology
Exotoxins
/ immunology
HLA Antigens
/ genetics
Humans
Mice
Mice, Inbred BALB C
Mice, Transgenic
Shock, Septic
/ genetics
Streptococcal Infections
/ genetics
Streptococcus pyogenes
/ immunology
Superantigens
/ immunology
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
11
03
2019
accepted:
07
08
2019
entrez:
14
9
2019
pubmed:
14
9
2019
medline:
15
5
2020
Statut:
epublish
Résumé
Invasive streptococcal disease (ISD) and toxic shock syndrome (STSS) result in over 160,000 deaths each year. We modelled these in HLA-transgenic mice infected with a clinically lethal isolate expressing Streptococcal pyrogenic exotoxin (Spe) C and demonstrate that both SpeC and streptococcal M protein, acting cooperatively, are required for disease. Vaccination with a conserved M protein peptide, J8, protects against STSS by causing a dramatic reduction in bacterial burden associated with the absence of SpeC and inflammatory cytokines in the blood. Furthermore, passive immunotherapy with antibodies to J8 quickly resolves established disease by clearing the infection and ablating the inflammatory activity of the M protein, which is further enhanced by addition of SpeC antibodies. Analysis of 77 recent isolates of
Identifiants
pubmed: 31517054
doi: 10.1126/sciadv.aax3013
pii: aax3013
pmc: PMC6726444
doi:
Substances chimiques
Antibodies, Bacterial
0
Antigens, Bacterial
0
Bacterial Outer Membrane Proteins
0
Bacterial Proteins
0
Carrier Proteins
0
Exotoxins
0
HLA Antigens
0
Superantigens
0
erythrogenic toxin
0
streptococcal M protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaax3013Références
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