| First Author | Thompson AL | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 6 | Pages | 2834-46 |
| PubMed ID | 22345651 | Mgi Jnum | J:181839 |
| Mgi Id | MGI:5314267 | Doi | 10.4049/jimmunol.1100254 |
| Citation | Thompson AL, et al. (2012) Maximal Adjuvant Activity of Nasally Delivered IL-1alpha Requires Adjuvant-Responsive CD11c+ Cells and Does Not Correlate with Adjuvant-Induced In Vivo Cytokine Production. J Immunol 188(6):2834-46 |
| abstractText | IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered IL-1alpha as determined by the acute induction of cytokine responses and induction of Bacillus anthracis lethal factor (LF)-specific adaptive immunity. Cytokine and chemokine responses induced by vaccination with IL-1alpha were predominantly derived from the stromal cell compartment and included G-CSF, IL-6, IL-13, MCP-1, and keratinocyte chemoattractant. Nasal vaccination of Il1r1(-/-) (knock-out [KO]) mice given wild-type (WT) BM (WT-->KO) and WT-->WT mice with LF + IL-1alpha induced maximal adaptive immune responses, whereas vaccination of WT mice given Il1r1(-/-) BM (KO-->WT) resulted in significantly decreased production of LF-specific serum IgG, IgG subclasses, lethal toxin-neutralizing Abs, and mucosal IgA compared with WT-->KO and WT-->WT mice (p < 0.05). IL-1alpha adjuvant activity was not dependent on mast cells. However, the ability of IL-1alpha to induce serum LF-specific IgG2c and lethal toxin-neutralizing Abs was significantly impaired in CD11c-Myd88(-/-) mice when compared with WT mice (p < 0.05). Our results suggest that CD11c(+) cells must be directly activated by nasally administered IL-1alpha for maximal adjuvant activity and that, although stromal cells are required for maximal adjuvant-induced cytokine production, the adjuvant-induced stromal cell cytokine responses are not required for effective induction of adaptive immunity. |
