Walking the tightrope: Balancing immune checkpoints and their inhibitors in host defence against bacterial infections

Immune checkpoints are one of the mechanisms that maintain the balance between immunotolerance and immunopathology. These mechanisms are often exploited by tumour cells. Thanks to extensive global testing of anticancer drugs, a revolutionary cancer therapy based on immune checkpoint inhibitors (ICIs) has been developed. Some pathogens exploit regulatory checkpoint interactions, contributing to the establishment of hidden, long-term, or persistent infections in which the host is unable to eliminate the pathogen. However, a structured overview of immune checkpoint involvement in bacterial infections remains underrepresented in the current scientific literature. We conducted a literature review focusing on the documented role of selected immune checkpoints (specifically PD-1, PD-L1, TIM-3, LAG-3, CTLA-4, and TIGIT) during infections of humans and animals with clinically relevant bacterial pathogens from the Actinobacteria, Chlamydiae, Firmicutes, Proteobacteria, and Spirochaetae phyla. The current state of knowledge suggests that applied research into immune checkpoints and the controlled use of ICIs has great potential to improve the diagnosis, treatment, and prognosis of serious human bacterial infections.