Bacterial Immune Evasion through Manipulation of Host Inhibitory Immune Signaling

Abstract

An innate immune response is essential for survival of the host upon infection, yet excessive inflammation can result in harmful complications [1]. Inhibitory signaling evolved to limit host responses and prevent inflammatory pathology [2,3]. Given the significance of inhibitory pathways for immunity and homeostasis, they provide ideal targets for manipulation by bacterial pathogens. Recent evidence highlights that bacteria have developed diverse strategies to exploit these inhibitory pathways to avoid host defense for their own benefit. In this review, we cover these different immune evasion strategies for the first time. The recent literature discussed emphasizes that bacteria subvert host immune responses not only by direct engagement of inhibitory receptors (i.e., often through "molecular mimicry" of host ligands [4,5]) but also through virulence factors that resemble intermediates of host inhibitory signaling and interfere with defense functions [6-8]. Understanding how bacteria manipulate inhibitory signaling affords promising opportunities to counteract these escape strategies and tip the balance in favor of the host. In addition, these understandings may provide useful insights on the functional roles of inhibitory pathways in limiting host responses and preventing pathology.