CD8+T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection

Scrub typhus,caused by a gram-negative obligately intracellular coccobacillus,orientia tsutsugamushi,is a long neglected but important tropical disease. orientia tsutsugamushi causes illness in one million people each year,and 1 billion people are at risk. without appropriate diagnosis and treatment,the disease can cause severe multiorgan failure with a case fatality rate of 7–15%. the current gaps in knowledge of immunity include the unknown mechanisms of host immunity to o. tsutsugamushi. using an intravenous (i.v.) disseminated infection mouse model,we observed that more cd8+t cells than cd4+t cells were present in the spleen of infected mice at 12 dpi. we also determined that tregcells and the proportion of t cells producing il-10 were significantly increased from 6 dpi,which correlated with the onset of illness,body weight loss,and increased bacterial loads. we further studied cd8-/-,mhc i-/-and wild type control (wt) c57bl/6j mice to determine the importance of cd8+t cells and mhc i molecules. after infection with an ordinarily sub-lethal dose of o. tsutsugamushi,all cd8-/-and mhc i-/-mice were moribund between 12 and 15 dpi,whereas all wt mice survived. bacterial loads in the lung,kidney,liver and spleen of cd8-/-and mhc i-/-mice were significantly greater than those in wt mice. interferon-γ (ifn-γ) and granzyme b mrna levels in the liver of cd8-/-and mhc i-/-mice were significantly greater than in wt mice. in addition,more severe histopathologic lesions were observed in cd8-/-mice. finally,adoptive transfer confirmed a major role of immune cd8+t cells as well as a less effective contribution by immune cd8 t cell-depleted splenocytes in protection against o. tsutsugamushi infection. these studies demonstrated the critical importance of cd8+t cells in the host immune response during o. tsutsugamushi infection. © 2017 xu et al.