| First Author | Oleszycka E | Year | 2016 |
| Journal | FEBS J | Volume | 283 |
| Issue | 1 | Pages | 9-24 |
| PubMed ID | 26536497 | Mgi Jnum | J:252289 |
| Mgi Id | MGI:6093284 | Doi | 10.1111/febs.13546 |
| Citation | Oleszycka E, et al. (2016) IL-1alpha and inflammasome-independent IL-1beta promote neutrophil infiltration following alum vaccination. FEBS J 283(1):9-24 |
| abstractText | Despite its long record of successful use in human vaccines, the mechanisms underlying the immunomodulatory effects of alum are not fully understood. Alum is a potent inducer of interleukin-1 (IL-1) secretion in vitro in dendritic cells and macrophages via Nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome activation. However, the contribution of IL-1 to alum-induced innate and adaptive immune responses is controversial and the role of IL-1alpha following alum injection has not been addressed. This study shows that IL-1 is dispensable for alum-induced antibody and CD8 T cell responses to ovalbumin. However, IL-1 is essential for neutrophil infiltration into the injection site, while recruitment of inflammatory monocytes and eosinophils is IL-1 independent. Both IL-1alpha and IL-1beta are released at the site of injection and contribute to the neutrophil response. Surprisingly, these effects are NLRP3-inflammasome independent as is the infiltration of other cell populations. However, while NLRP3 and caspase 1 were dispensable, alum-induced IL-1beta at the injection site was dependent on the cysteine protease cathepsin S. Overall, these data demonstrate a previously unreported role for cathepsin S in IL-1beta secretion, show that inflammasome formation is dispensable for alum-induced innate immunity and reveal that IL-1alpha and IL-1beta are both necessary for alum-induced neutrophil influx in vivo. |
