Release and Innate detection of host cell DNA mediates the adjuvant effects of aluminum salts on adaptive responses

in Proceedings of the 1St Winter School Immunology (2012, January)

DNA released from dying host cells mediates aluminum adjuvant activity

in Nature Medicine (2011), 17

Aluminum-based adjuvants (alum) are widely used in human vaccination, although little is understood of their mechanisms of action. Here, we report that, in mice, alum causes the release of host cell DNA ... [more ▼]

Aluminum-based adjuvants (alum) are widely used in human vaccination, although little is understood of their mechanisms of action. Here, we report that, in mice, alum causes the release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production upon alum immunization. Indeed, we support that host DNA induces primary B cell responses, including IgG1 production, through Interferon Response Factor (Irf) 3-independent mechanisms, and 'canonical' type 2 T cell responses associated with IgE isotype switching and peripheral effector responses through Irf3-dependent mechanisms. The finding that host cell DNA is a damage-associated molecular pattern relaying alum adjuvant activity may thus help in the comprehension of the mechanisms of action of current vaccines and in the design of novel adjuvants. [less ▲]

IRF3-dependent activation of inflammatory dendritic cells by extracellular host DNA mediates the adjuvant activity of alum on TH2 responses

Poster (2011)

Release and innate immune detection of host cell DNA mediate the adjuvant activity of aluminum salts

Poster (2011)

Self-DNA release mediates the adjuvant effects of aluminum salts

Poster (2011)

Viral induction of Zac1b through TLR3- and IRF3-dependent pathways

in Molecular Immunology (2010), 48(1-3), 119-127

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important ... [more ▼]

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important potential functions attributed to Zac1, little is known of its physiological regulation and biological function. We discovered that variant Zac1b was expressed in murine embryonic fibroblasts (MEFs) treated with polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA. This regulation occurred mainly through Toll-Like Receptor 3 (TLR3)- and Interferon Regulatory Factor 3 (IRF3)-dependent pathways. As TLR3 and IRF3 are central activators of antiviral immunity, we hypothesized that Zac1 may be implicated in antiviral responses. In line with this notion, we observed that Zac1b was expressed in MEFs infected with Encephalomyocarditis virus (EMCV). We also observed that Zac1-deficient MEFs were less sensitive to EMCV-induced cell death than wild-type MEFs. However, Zac1 gene inactivation had no effect on the survival of mice infected with EMCV. In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated. [less ▲]

Tableau clinique et mécanismes physiopathologiques des principales maladies inflammatoires chroniques des voies respiratoires du cheval

in Annales de Médecine Vétérinaire (2006), 150(4), 227-240

The respiratory tract of the horse can be the seat of several chronic inflammatory diseases whose principal ones are the recurrent airway obstruction, the inflammatory airway disease, the summer pasture ... [more ▼]

The respiratory tract of the horse can be the seat of several chronic inflammatory diseases whose principal ones are the recurrent airway obstruction, the inflammatory airway disease, the summer pasture-associated obstructive pulmonary disease and the follicular pharyngitis. These diseases can have an important impact on horses’ health and on their sports performances. A good knowledge of their aetiologies and their physiopathological mechanisms would allow a better control of these affections. However, even if many studies were made on this subject, there are currently very few certainties as for the inflammatory mechanisms governing these diseases. This article aims to make an inventory of knowledge and deficiencies concerning these four chronic inflammatory diseases [less ▲]