DNA released from dying host cells mediates aluminum adjuvant activity
DNA released from dying host cells mediates aluminum adjuvant activity
Marichal, T. et al. 2011. Nat. Med. 17:996-1002.
Student: Yi-Jui Chuang (莊宜叡) -- Time: 13:10-14:00, Oct. 19, 2011
Commentator: Dr. Yee-Shin Lin (林以行 博士) Place: Room 601
Abstract
It is unclear the detail mechanism of aluminum (alum)-based adjuvant used in human vaccination. Alum treatment exerts cytotoxicity [1] and may cause the release of damage-associated molecular pattern (DAMP), a regulator for innate immune system through pattern-recognition receptors, from dying host cells. It the present work, the authors investigated whether DAMP contributes to the adjuvants effect of alum on humoral responses in vivo. They found that alum caused cell death and increased the release of soluble double-stranded DNA (dsDNA), dose-dependently. After alum treatment, the soluble dsDNA released from dying host cell triggered humoral and TH2 cell responses in an interferon response factor (IRF) 3-dependent manner regarding most of the host DNA-activated pathways lead to IRF3 activation [2]. There was a reduction number of inflammatorymonocyte (iMono)-derived inflammatory dendritic cells (iDCs) in the draining lymph nodes of alum-treated Irf3-/- mice. Recent evidence indicates that iMono-derived DCs depend on signaling of IL-12p80 for their ability to respond to chemokines [3]. Alum induced the local production of IL-12p80 was lower in Irf3-/- mice than in wild-type mice, suggesting the IL-12p80-mediated alum-induced iDC activation. In conclusion, these results show that host DNA released from dying host cell act as a DAMP to alert immune cells, which may increase the contact between antigen and antigen presenting cells and activate humoral responses.
References
1. Goto, N. et al. 1997. Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminum hydroxide with different physical properties. Vaccine. 15:1364-1371.
2. Chiu, Y. H. et al. 2009. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 138:576-591.
3. Khader, S. A. et al. 2006. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. J. Exp. Med. 203:1805-1815.