Figure 3.

An example of the relationship between immune defenses and bacterial biofilm is summarized, in which c-di-NMPs are involved. Biofilms produce c-di-NMPs. c-di-NMPs stimulate the synthesis of biofilm matrix components. Host cells sense c-di-NMPs as PAMPs. As a result, an immune response is generated to eliminate pathogens. But, the biofilm matrix protects biofilm bacteria as a shield against phagocytosis and antibody deposition by plasma cells. Furthermore, biofilm induces the reprogramming of macrophages towards an M2 phenotype, characterized by poor microbicidal activity, and the recruitment of myeloid-derived suppressor cells (MDSCs) [142]. MDSCs produce the immunosuppressive molecule interleukin-10 (IL-10), which attenuates the immune response and contributes to biofilm persistence. Some bacteria within biofilms can be phagocytosed by immune cells but resist ROS and AMPs (such as defensins 3 and LL-37) thanks to the polysaccharides of their matrix [27,143,144,145]. They can survive intracellularly, thus contributing to the chronic nature of biofilm-associated infections. Abbreviations: c-di-NMPs, cyclic dinucleotides (intracellular signaling second-messenger systems); MØ, macrophages; IFN-γ, interferon-γ; NK, natural killer cells; PAMPs, pathogen-associated molecular patterns; T cells, T lymphocytes; B cells, B lymphocytes/plasma cells (plasma cells derive from B lymphocytes after encountering the antigen); Ab, antibodies; PMNs, polymorphonuclear neutrophils; AMPs, antimicrobial peptides; ROS, reactive oxygen species.