Pattern Recognition Receptors in Innate Immunity to Obligate Intracellular Bacteria

Host pattern recognition receptors (PRRs) are crucial for sensing pathogenic microorganisms, initiating innate responses, and modulating pathogen-specific adaptive immunity during infection. Rickettsia spp., Orientia tsutsugamushi, Anaplasma spp., Ehrlichia spp., and Coxiella burnetii are obligate intracellular bacteria that can replicate only within host cells and must evade immune detection to successfully propagate. These five bacterial species are zoonotic pathogens of clinical or agricultural importance, yet uncovering how immune recognition occurs has remained challenging. Recent evidence from in vitro studies and animal models has yielded new insights into the types and kinetics of PRR activation during infection with Rickettsia spp., A. phagocytophilum, E. chaffeensis, and C. burnetii. However, much less was known about PRR activation in O. tsutsugamushi infection until the recent discovery of the role of the C-type lectin receptor Mincle during lethal infection in mice and in primary macrophage cultures. This review provides a brief summary of the clinical and epidemiologic features of these five bacterial infections, with a focus on the fundamental biologic facets of infection, and recent advances in host recognition. In addition, knowledge gaps regarding the innate recognition of these bacteria in the context of disease pathogenesis are discussed.