[The intestinal flora: the scales without the sword]. / La Flore intestinale commensale: la balance sans le glaive?

The intestine is colonised by a vast population of resident bacteria which have established mutualistic relationships with their host throughout evolution, progressing from commensalism to symbiotic interactions. Intestinal bacteria benefit from resources available in their host, but reciprocally provide advantages to their host, by supplying enzymatic activities not encoded in the host genome, by promoting maturation of the intestine and of the gut associated immune system as well as by modifying the host metabolism. The commensal bacteria, although deprived of pathogenic attributes, might however become a danger for the host in case of translocation, acquisition of pathogenic features or via the inappropriate activation of intestinal inflammation. Remarkably, the commensal flora promotes the onset of innate and adaptive immune defences which, in turn, allow to set up a subtle balance between the host and the flora that promotes the symbiosis.

TLR9 pathway is involved in adjuvant effects of plasmid DNA-based vaccines.

The presence of unmethylated CpG motifs in bacterial plasmids is thought to provide necessary immunoadjuvant signals to DNA vaccination. We took advantage of CpG-unresponsive toll-like receptor 9 (TLR9) knock-out mice to study whether this pathway was required to generate immune responses to DNA vaccination. We compared two vectors, one encoding the surface glycoprotein C of pseudorabies virus shown to protect target animals against challenge, and the other encoding the cytoplasmic enzyme beta-galactosidase. In the absence of TLR9, bone marrow-derived dendritic cells lost their ability to secrete IL-12 and type I IFN in response not only to CpG as expected but also to the plasmids used for vaccination. In contrast, DNA vaccination experiments showed that TLR9-deficient mice were able to mount Th1-biased antigen-specific antibody and IFN-gamma responses, albeit at lower levels than normal mice. Thus, TLR9 signaling is not needed for eliciting T- and B-cell responses to DNA encoded antigens. However, TLR9 signaling tended to enhance plasmid-adjuvant effects on antigen-specific immune responses.