Figure 1.

Roles of the T6SS in host-microbiota-pathogen interactions. In healthy steady state conditions (middle panel), commensal bacteria use the T6SS to establish and maintain their niche in the host. The release of MAMPs through T6SS warfare can contribute to the establishment of immune tolerance, enhancing the symbiotic relationship. In the case of host immune deficiency (right panel), for example due to a genetic polymorphism in the host, cross-talk with the microbiota is compromised and the balance within the microbial community may be disrupted, resulting in chronic dysbiosis. The T6SS is likely to play a role in the modulation of competing commensal populations and subsequent decrease in diversity of bacteria phyla, as well as potentially directly manipulating host cells. In the case of infection by pathogenic bacteria wielding a T6SS (left panel), commensal bacteria are eliminated through both direct delivery of antibacterial effectors and indirect mechanisms such as host manipulation and nutrient competition. The state of dysbiosis that follows is acute but may be resolved through elimination of the pathogen by the host immune system. In both states of dysbiosis, the T6SS may play a determining role in eliciting the release of DAMPs, which influences the host immune response.