Pathogenic Rickettsia species evade autophagosomal maturation and reduce anti-microbicidal pro-inflammatory IL-1 responses to support their intracellular survival.

Species of genus Rickettsia are obligate intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some Rickettsia species are responsible for several serious human diseases. One fascinating feature of these stealthy group of pathogens is their ability to exploit host cytosolic defense responses to their benefits. However, the precise mechanism by which pathogenic Rickettsia elude host immune defense responses remains to be determined. Here, we observed that pathogenic R. typhi and R. rickettsii, but not non-pathogenic R. montanensis become ubiquitinated and induce autophagy upon entry into bone-marrow-derived macrophages. Moreover, unlike R. montanensis, R. typhi, and R. rickettsii colocalized with LC3B but not with Lamp2 upon host cell entry. Finally, we observed that pathogenic but not non-pathogenic Rickettsia reduce pro-inflammatory IL-1 responses. In sum, we identified a previously unappreciated pathway by which pathogenic, but not non-pathogenic, Rickettsia become ubiquitinated and induced autophagy, but avoided autophagolysosomal destruction as well as inflammasome-mediated anti-microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages.