Innate immune defenses against a cytosolic capsule

Duke University, Durham NC

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Abstract

Abstract All pathogens evolve virulence mechanism to evade immune responses, especially those that would most directly counteract their virulence. Simultaneously, host species evolve defenses against pathogenic virulence properties. This never-ending competition is an example of the Red Queen’s evolutionary race. However, at each point in the competition one side may have the upper hand. We have often found that pathogens have the upper hand over immune defenses, which allows the bacterium to replicate and cause disease until an adaptive immune response turns the tide. In contrast, our lab has found that environmental bacteria often have strong virulence potential, but lack the evasive properties of host-adapted pathogens. These “Red Pawns” are readily eliminated by immune defenses. In this grant, we discover a new Red Pawn environmental pathogen that has a strong virulence potential conferred by an extracellular polysaccharide capsule – however, this virulence benefit comes at the cost of being readily detected by immune sensors that organize successful countermeasures against the capsule. Many bacteria produce extracellular polysaccharides that form a capsule. Such capsules allow bacteria to evade the immune response. Capsules can prevent complement deposition to allow bacteria to evade the extracellular complement deposition that could opsonize bacteria and attract phagocytes from the immune system. Capsules also shield other cell surface molecules that allow phagocytes to bind and phagocytose bacteria. Thus, capsules have been a classical virulence trait that allows bacteria to replicate in the extracellular space by resisting extracellular defenses. However, extracellular polysaccharides have also been identified on bacteria that are invasive and replicate intracellularly. Here we study how intracellular capsule provides a virulence benefit to an intracellular environmental bacterial pathogen, and how the host immune system senses this virulence trait and responds to counteract the virulence of the bacterium.