Pattern Recognition Receptors in Innate Immunity to Obligate Intracellular Bacteria

Host pattern recognition receptors (PRRs) are crucial for sensing pathogenic microorganisms, launching innate responses, and shaping pathogen-specific adaptive immunity during infection. Rickettsia spp., Orientia tsutsugamushi, Anaplasma spp., Ehrlichia spp., and Coxiella burnetii are obligate intracellular bacteria, which can only replicate 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 offered new insights into the types and kinetics of PRR activation during infection with Rickettsia spp., A. phagocytophilum, E. chaffeensis, and C. burnetii, respectively. However, much less is known in these regards for O. tsutsugamushi infection, until the recent discovery for the role of the C-type lectin receptor Mincle during lethal infection in mice and in primary macrophage cultures. This review gives a brief summary for clinical and epidemiologic features of these five bacterial infections, focuses on fundamental biologic facets of infection, and recent advances in host recognition. In addition, we discuss knowledge gaps for innate recognition of these bacteria in the context of disease pathogenesis.