TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion.
Toll like receptor 4 (TLR4) is an important pattern recognition receptor with the ability to drive potent innate immune responses and also to modulate adaptive immune responses needed for long term protection. Activation of TLR4 by its ligands is mediated by engagement of the adapter proteins MyD88...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3574014?pdf=render |
| _version_ | 1811196930074607616 |
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| author | Siva K Gandhapudi Paula M Chilton Thomas C Mitchell |
| author_facet | Siva K Gandhapudi Paula M Chilton Thomas C Mitchell |
| author_sort | Siva K Gandhapudi |
| collection | DOAJ |
| description | Toll like receptor 4 (TLR4) is an important pattern recognition receptor with the ability to drive potent innate immune responses and also to modulate adaptive immune responses needed for long term protection. Activation of TLR4 by its ligands is mediated by engagement of the adapter proteins MyD88 (myeloid differentiation factor 88) and TRIF (Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta). Previously, we showed that TRIF, but not MyD88, plays an important role in allowing TLR4 agonists to adjuvant early T cell responses. In this study, we investigated the T cell priming events that are regulated specifically by the TRIF signaling branch of TLR4. We found that TRIF deficiency prevented the TLR4 agonist lipid A from enhancing T cell proliferation and survival in an adoptive transfer model of T cell priming. TRIF deficient DC showed defective maturation as evidenced by their failure to upregulate co-stimulatory molecules in response to lipid A stimulation. Importantly, TRIF alone caused CD86 and CD40 upregulation on splenic DC, but both TRIF and MyD88 were required for CD80 upregulation. The impairment of T cell adjuvant effects and defective DC maturation in TRIF (lps/lps) mice after TLR4 stimulation was mainly due to loss of type I IFN production, indicating that type I interferons are central to TLR4's adjuvant effects. These results are useful for the continued development of TLR4 based vaccine adjuvants that avoid inflammatory risks while retaining beneficial immune response. |
| first_indexed | 2024-04-12T01:06:56Z |
| format | Article |
| id | doaj.art-b55007ab3cd348daa46501a66805f4ab |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T01:06:56Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b55007ab3cd348daa46501a66805f4ab2022-12-22T03:54:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5685510.1371/journal.pone.0056855TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion.Siva K GandhapudiPaula M ChiltonThomas C MitchellToll like receptor 4 (TLR4) is an important pattern recognition receptor with the ability to drive potent innate immune responses and also to modulate adaptive immune responses needed for long term protection. Activation of TLR4 by its ligands is mediated by engagement of the adapter proteins MyD88 (myeloid differentiation factor 88) and TRIF (Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta). Previously, we showed that TRIF, but not MyD88, plays an important role in allowing TLR4 agonists to adjuvant early T cell responses. In this study, we investigated the T cell priming events that are regulated specifically by the TRIF signaling branch of TLR4. We found that TRIF deficiency prevented the TLR4 agonist lipid A from enhancing T cell proliferation and survival in an adoptive transfer model of T cell priming. TRIF deficient DC showed defective maturation as evidenced by their failure to upregulate co-stimulatory molecules in response to lipid A stimulation. Importantly, TRIF alone caused CD86 and CD40 upregulation on splenic DC, but both TRIF and MyD88 were required for CD80 upregulation. The impairment of T cell adjuvant effects and defective DC maturation in TRIF (lps/lps) mice after TLR4 stimulation was mainly due to loss of type I IFN production, indicating that type I interferons are central to TLR4's adjuvant effects. These results are useful for the continued development of TLR4 based vaccine adjuvants that avoid inflammatory risks while retaining beneficial immune response.http://europepmc.org/articles/PMC3574014?pdf=render |
| spellingShingle | Siva K Gandhapudi Paula M Chilton Thomas C Mitchell TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion. PLoS ONE |
| title | TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion. |
| title_full | TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion. |
| title_fullStr | TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion. |
| title_full_unstemmed | TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion. |
| title_short | TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion. |
| title_sort | trif is required for tlr4 mediated adjuvant effects on t cell clonal expansion |
| url | http://europepmc.org/articles/PMC3574014?pdf=render |
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