| First Author | Vijay-Kumar M | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 12 | Pages | 3528-34 |
| PubMed ID | 21072873 | Mgi Jnum | J:174469 |
| Mgi Id | MGI:5086070 | Doi | 10.1002/eji.201040421 |
| Citation | Vijay-Kumar M, et al. (2010) TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin. Eur J Immunol 40(12):3528-34 |
| abstractText | The fact that some TLR-based vaccine adjuvants maintain function in TLR-deficient hosts highlights that their mechanism of function remains incompletely understood. Thus, we examined the ability of flagellin to induce cytokines and elicit/promote murine antibody responses upon deletion of the flagellin receptors TLR5 and/or NLRC4 (also referred to as IPAF) using a prime/boost regimen. In TLR5-KO mice, flagellin failed to induce NF-kappaB-regulated cytokines such as keratinocyte-derived chemokine (CXCL1) but induced WT levels of the inflammasome cytokine IL-18 (IL-1F4). Conversely, in NLRC4-KO mice, flagellin induced keratinocyte-derived chemokine, but not IL-18, whereas TLR5/NLRC4-DKO lacked induction of all cytokines measured. Flagellin/ovalbumin treatment resulted in high-antibody titers to both flagellin and ovalbumin in WT, TLR5-KO and DKO mice but did not elicit antibodies to either in TLR5/NLRC4-DKO mice. Thus, flagellin's ability to elicit/promote humoral immunity requires a germ-line-encoded receptor capable of recognizing this molecule. Such promotion of adaptive immunity can be effectively driven by either TLR5-mediated activation of NF-kappaB or NLRC4-mediated activation of the inflammasome. |
