Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 8, Pages 2085-2089Publisher
WILEY
DOI: 10.1002/eji.200838549
Keywords
adjuvant; aluminum hydroxide; caspase-1; NOD-like receptor
Categories
Funding
- NIH [AI063331, AI064748]
- Arthritis Foundation
Ask authors/readers for more resources
Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines, but the immune mechanisms that are activated by alum remain poorly understood. Alum has recently been shown to promote caspase-1 activation and IL-1P secretion, but the cellular pathways involved remain elusive. Here we report that the release of IL-1p triggered by alum is abrogated in macrophages deficient in the NLR family, pyrin domain containing 3 (NIrp3) protein and the apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) but not the NLR family, CARD domain containing 4 (Nlrc4) protein. The requirement of the Nlrp3 inflammasome was specific for IL-1p in that secretion of TNF-alpha was independent of NIrp3 or Asc. Consistently, processing of pro-caspase-1 induced by alum was abolished in macrophages lacking Nlrp3 or Asc. Unlike caspase-1 processing and IL-1 beta secretion triggered by LPS, alum-mediated activation of the inflammasome did not require exogenous ATP. Importantly, induction of IgG production against human serum albumin by alum was unimpaired in mice deficient in Nlrp3. These results indicate that alum induces IL-10 via the Nlrp3 inflammasome but this activity is dispensable for alum-mediated adjuvant activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available