Abstract
Innate immune activation via TLR induces dendritic cell maturation and secretion of inflammatory mediators, generating favorable conditions for naïve T-cell activation. Here, we demonstrate a previously unknown function for TLR5, namely that it enhances MHC class-II presentation of flagellin epitopes to CD4+ T cells and is required for induction of robust flagellin-specific adaptive immune responses. Flagellin-specific CD4+ T cells expanded poorly in TLR5-deficient mice immunized with flagellin, a deficiency that persisted even when additional TLR agonists were provided. Flagellin-specific IgG responses were similarly depressed in the absence of TLR5. In marked contrast, TLR5-deficient mice developed robust flagellin-specific T-cell responses when immunized with processed flagellin peptide. Surprisingly, the adaptor molecule Myd88 was not required for robust CD4+ T-cell responses to flagellin, indicating that TLR5 enhances flagellin-specific CD4+ T-cell responses in the absence of conventional TLR signaling. A requirement for TLR5 in generating flagellin-specific CD4+ T-cell activation was also observed when using an in vitro dendritic cell culture system. Together, these data uncover an Myd88-independent function for dendritic cell TLR5 in enhancing the presentation of peptides to flagellin-specific CD4+ T cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 29-38 |
| Number of pages | 10 |
| Journal | European Journal of Immunology |
| Volume | 41 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2011 |
| Externally published | Yes |
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Keywords
- CD4 T cells
- Dendritic cells
- TLR
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. / Letran, Shirdi E.; Lee, Seung Joo; Atif, Shaikh M.; Uematsu, Satoshi; Akira, Shizuo; Mcsorley, Stephen J.
In: European Journal of Immunology, Vol. 41, No. 1, 01.2011, p. 29-38.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity
AU - Letran, Shirdi E.
AU - Lee, Seung Joo
AU - Atif, Shaikh M.
AU - Uematsu, Satoshi
AU - Akira, Shizuo
AU - Mcsorley, Stephen J
PY - 2011/1
Y1 - 2011/1
N2 - Innate immune activation via TLR induces dendritic cell maturation and secretion of inflammatory mediators, generating favorable conditions for naïve T-cell activation. Here, we demonstrate a previously unknown function for TLR5, namely that it enhances MHC class-II presentation of flagellin epitopes to CD4+ T cells and is required for induction of robust flagellin-specific adaptive immune responses. Flagellin-specific CD4+ T cells expanded poorly in TLR5-deficient mice immunized with flagellin, a deficiency that persisted even when additional TLR agonists were provided. Flagellin-specific IgG responses were similarly depressed in the absence of TLR5. In marked contrast, TLR5-deficient mice developed robust flagellin-specific T-cell responses when immunized with processed flagellin peptide. Surprisingly, the adaptor molecule Myd88 was not required for robust CD4+ T-cell responses to flagellin, indicating that TLR5 enhances flagellin-specific CD4+ T-cell responses in the absence of conventional TLR signaling. A requirement for TLR5 in generating flagellin-specific CD4+ T-cell activation was also observed when using an in vitro dendritic cell culture system. Together, these data uncover an Myd88-independent function for dendritic cell TLR5 in enhancing the presentation of peptides to flagellin-specific CD4+ T cells.
AB - Innate immune activation via TLR induces dendritic cell maturation and secretion of inflammatory mediators, generating favorable conditions for naïve T-cell activation. Here, we demonstrate a previously unknown function for TLR5, namely that it enhances MHC class-II presentation of flagellin epitopes to CD4+ T cells and is required for induction of robust flagellin-specific adaptive immune responses. Flagellin-specific CD4+ T cells expanded poorly in TLR5-deficient mice immunized with flagellin, a deficiency that persisted even when additional TLR agonists were provided. Flagellin-specific IgG responses were similarly depressed in the absence of TLR5. In marked contrast, TLR5-deficient mice developed robust flagellin-specific T-cell responses when immunized with processed flagellin peptide. Surprisingly, the adaptor molecule Myd88 was not required for robust CD4+ T-cell responses to flagellin, indicating that TLR5 enhances flagellin-specific CD4+ T-cell responses in the absence of conventional TLR signaling. A requirement for TLR5 in generating flagellin-specific CD4+ T-cell activation was also observed when using an in vitro dendritic cell culture system. Together, these data uncover an Myd88-independent function for dendritic cell TLR5 in enhancing the presentation of peptides to flagellin-specific CD4+ T cells.
KW - CD4 T cells
KW - Dendritic cells
KW - TLR
UR - http://www.scopus.com/inward/record.url?scp=78650368903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650368903&partnerID=8YFLogxK
U2 - 10.1002/eji.201040717
DO - 10.1002/eji.201040717
M3 - Article
C2 - 21182074
AN - SCOPUS:78650368903
VL - 41
SP - 29
EP - 38
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -