Flagellin is a Th1 polarizing factor for human CD4+ T cells and induces protection in a murine neonatal vaccination model of rotavirus infection.
Vaccine
; 36(29): 4188-4197, 2018 07 05.
Article
em En
| MEDLINE
| ID: mdl-29891347
Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4+ T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates. Among them, flagellin, the TLR5 ligand, is effective at very low doses; prior immunity to flagellin does not impair its adjuvant activity. Human CD4+ and CD8+ T cells express TLR5. We found that flagellin induces the expression of IFN-γ, IL-1ß and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4+ T cells were activated in the presence of flagellin, there was high level of expression of IFN-γ in both neonates and adults. Furthermore, flagellin induced IFN-γ production in Th1 cells obtained from adult donors; in the Th2 population, it inhibited IL-4 cytokine production. Flagellin also promoted expression of the IFN-γ receptor in naive CD4+ T cells from neonates and adults. To test the adjuvant capacity of flagellin in vivo, we used a murine neonate vaccination model for infection with rotavirus, a pathogen responsible for severe diarrhea in young infants. Using the conserved VP6 antigen, we observed an 80% protection against rotavirus infection in the presence of flagellin, but only in those mice previously primed in the neonatal period. Our data suggest that flagellin could be an attractive adjuvant for achieving a Th1 response.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por Rotavirus
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Adjuvantes Imunológicos
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Rotavirus
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Células Th1
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Vacinas contra Rotavirus
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Flagelina
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Newborn
Idioma:
En
Revista:
Vaccine
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Holanda