Integrated Signaling Pathways Mediate Bordetella Immunomodulation, Persistence, and Transmission

Abstract

The mammalian immune system includes a sophisticated array of antimicrobial mechanisms. However, successful pathogens have developed subversive strategies to detect, modulate, and/or evade immune control and clearance. Independent disciplines study host immunology and bacterial pathogenesis, but interkingdom signaling between bacteria and host during natural infection remains poorly understood. An efficient natural host infection system has revealed complex communication between Bordetella spp. and mice, identified novel regulatory mechanisms, and demonstrated that bordetellae can respond to microenvironment and inflammatory status cues. Understanding these bacterial signaling pathways and their complex network that allows precisely timed expression of numerous immunomodulatory factors will serve as a paradigm for other organisms lacking such a powerful experimental infection system. VIDEO ABSTRACT.

Keywords: Bordetella spp.; immune response; immunomodulators; pathogenesis; signaling.

Figure 1:. Model of the molecular pathways of sensing and responding in Bordetella spp.

This figure is a schematic representation of the hypothetical connections between different Bordetella spp. regulatory mechanisms. The dotted lines indicate networks that are hypothetical. The bidirectional arrow indicates that the regulation can hypothetically go either way. The question mark indicates that there is no knowledge about the function of those regulators.

Figure 2:. Schematic of the known Bordetella spp. virulence factors and how these manipulate host immune response.

This figure shows how Bordetella changes gene expression (from blue to green), increasing expression of molecules (in black boxes) that down-regulate immune response.

Figure 3. (Key Figure): Different host microenvironments of Bordetella spp..

This figure indicates the different microenvironments within the host respiratory tract that Bordetella encounters and adapts to. The table shows the highlights of the different conditions.