Soluble flagellin, FliC, induces an Ag-specific Th2 response, yet promotes T-bet-regulated Th1 clearance of Salmonella Typhimurium infection.

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@article{8ed4d2ab086344bd9e7aa526f2ebfd35,
title = "Soluble flagellin, FliC, induces an Ag-specific Th2 response, yet promotes T-bet-regulated Th1 clearance of Salmonella Typhimurium infection.",
abstract = "Clearance of disseminated Salmonella infection requires bacterial-specific Th1 cells and IFNγproduction and Th1-promoting vaccines are likely to help control these infections. Consequently, vaccine design has focused on developing Th1-polarizing adjuvants or Ag that naturally induce Th1 responses. In this study we show that, in mice, immunization with soluble flagellin (sFliC) induces Th2 responses as evidenced by Ag-specific GATA-3, IL-4 mRNA and protein induction in CD62L(lo) CD4(+) T cells without associated IFNγ production. Despite these Th2 features, sFliC immunization can enhance the development of protective Th1 immunity during subsequent Salmonella infection in an Ab-independent, T cell-dependent manner. Salmonella infection in sFliC-immunized mice resulted in augmented Th1 responses, with greater bacterial clearance and increased numbers of IFNγ-producing CD4(+) T cells, despite the early induction of Th2 features to sFliC. The augmented Th1 immunity after sFliC immunization was regulated by T-bet although T-bet is dispensable for primary responses to sFliC. These findings show there can be flexibility in T cell responses to some subunit vaccines. These vaccines may induce Th2-type immunity during primary immunization yet promote Th1-dependent responses during later infection. This suggests that designing Th1-inducing subunit vaccines may not always be necessary since this can occur naturally during subsequent infection.",
keywords = "Flagellin, Salmonella, T-bet, T cells, Vaccine",
author = "Saeeda Bobat and Adriana Flores-Langarica and Jessica Hitchcock and Jennifer Marshall and RA Kingsley and M Goodall and C Gil-Cruz and Karine Serre and Denisse Leyton and SE Letran and Fabrina Gaspal and R Chester and Jayne Chamberlain and G Dougan and C L{\'o}pez-Mac{\'i}as and Ian Henderson and J Alexander and Ian MacLennan and Adam Cunningham",
year = "2011",
month = jun,
doi = "10.1002/eji.201041089",
language = "English",
volume = "41",
pages = "1606--1618",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "6",

}

RIS

TY - JOUR

T1 - Soluble flagellin, FliC, induces an Ag-specific Th2 response, yet promotes T-bet-regulated Th1 clearance of Salmonella Typhimurium infection.

AU - Bobat, Saeeda

AU - Flores-Langarica, Adriana

AU - Hitchcock, Jessica

AU - Marshall, Jennifer

AU - Kingsley, RA

AU - Goodall, M

AU - Gil-Cruz, C

AU - Serre, Karine

AU - Leyton, Denisse

AU - Letran, SE

AU - Gaspal, Fabrina

AU - Chester, R

AU - Chamberlain, Jayne

AU - Dougan, G

AU - López-Macías, C

AU - Henderson, Ian

AU - Alexander, J

AU - MacLennan, Ian

AU - Cunningham, Adam

PY - 2011/6

Y1 - 2011/6

N2 - Clearance of disseminated Salmonella infection requires bacterial-specific Th1 cells and IFNγproduction and Th1-promoting vaccines are likely to help control these infections. Consequently, vaccine design has focused on developing Th1-polarizing adjuvants or Ag that naturally induce Th1 responses. In this study we show that, in mice, immunization with soluble flagellin (sFliC) induces Th2 responses as evidenced by Ag-specific GATA-3, IL-4 mRNA and protein induction in CD62L(lo) CD4(+) T cells without associated IFNγ production. Despite these Th2 features, sFliC immunization can enhance the development of protective Th1 immunity during subsequent Salmonella infection in an Ab-independent, T cell-dependent manner. Salmonella infection in sFliC-immunized mice resulted in augmented Th1 responses, with greater bacterial clearance and increased numbers of IFNγ-producing CD4(+) T cells, despite the early induction of Th2 features to sFliC. The augmented Th1 immunity after sFliC immunization was regulated by T-bet although T-bet is dispensable for primary responses to sFliC. These findings show there can be flexibility in T cell responses to some subunit vaccines. These vaccines may induce Th2-type immunity during primary immunization yet promote Th1-dependent responses during later infection. This suggests that designing Th1-inducing subunit vaccines may not always be necessary since this can occur naturally during subsequent infection.

AB - Clearance of disseminated Salmonella infection requires bacterial-specific Th1 cells and IFNγproduction and Th1-promoting vaccines are likely to help control these infections. Consequently, vaccine design has focused on developing Th1-polarizing adjuvants or Ag that naturally induce Th1 responses. In this study we show that, in mice, immunization with soluble flagellin (sFliC) induces Th2 responses as evidenced by Ag-specific GATA-3, IL-4 mRNA and protein induction in CD62L(lo) CD4(+) T cells without associated IFNγ production. Despite these Th2 features, sFliC immunization can enhance the development of protective Th1 immunity during subsequent Salmonella infection in an Ab-independent, T cell-dependent manner. Salmonella infection in sFliC-immunized mice resulted in augmented Th1 responses, with greater bacterial clearance and increased numbers of IFNγ-producing CD4(+) T cells, despite the early induction of Th2 features to sFliC. The augmented Th1 immunity after sFliC immunization was regulated by T-bet although T-bet is dispensable for primary responses to sFliC. These findings show there can be flexibility in T cell responses to some subunit vaccines. These vaccines may induce Th2-type immunity during primary immunization yet promote Th1-dependent responses during later infection. This suggests that designing Th1-inducing subunit vaccines may not always be necessary since this can occur naturally during subsequent infection.

KW - Flagellin

KW - Salmonella

KW - T-bet

KW - T cells

KW - Vaccine

U2 - 10.1002/eji.201041089

DO - 10.1002/eji.201041089

M3 - Article

C2 - 21469112

VL - 41

SP - 1606

EP - 1618

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 6

ER -