Biofilm switch and immune response determinants at early stages of infection

• The biofilm state is a major virulence factor underlying chronic bacterial infections.
• High levels of cyclic dinucleotides induce the planktonic to biofilm switch in bacteria.
• Detection of cyclic dinucleotides triggers a type I interferon response in host cells.
• Cyclic dinucleotides could constitute biofilm-specific pathogen-associated molecular patterns (PAMPs).

Biofilm development is recognized as a major virulence factor underlying most chronic bacterial infections. When a biofilm community is established, planktonic cells growing in the surroundings of a tissue switch to a sessile lifestyle and start producing a biofilm matrix. The initial steps of in vivo biofilm development are poorly characterized and difficult to assess experimentally. A great amount of in vitro evidence has shown that accumulation of high levels of cyclic dinucleotides (c-di-NMPs) is the most prevalent hallmark governing the initiation of biofilm development by bacteria. As mentioned above, recent studies also link detection of c-di-NMPs by host cells with the activation of a type I interferon immune response against bacterial infections. We discuss here c-di-NMP signaling and the host immune response in the context of the initial steps of in vivo biofilm development.