The role of CD8 T lymphocytes in rickettsial infections

Abstract

Arthropod-borne obligately intracellular bacteria pose a difficult challenge to the immune system. The genera Rickettsia, Orientia, Ehrlichia, and Anaplasma evolved mechanisms of immune evasion, and each interacts differently with the immune system. The roles of CD8 T cells include protective immunity and immunopathology. In Rickettsia infections, CD8 T cells are protective mediated in part by cytotoxicity toward infected cells. In contrast, TNFα overproduction by CD8 T cells is pathogenic in lethal ehrlichiosis by induction of apoptosis/necrosis in hepatocytes. Yet, CD8 T cells, along with CD4 T cells and antibodies, also contribute to protective immunity in ehrlichial infections. In granulocytic anaplasmosis, CD8 T cells impact pathogen control modestly but could contribute to immunopathology by virtue of their dysfunction. While preliminary evidence indicates that CD8 T cells are important in protection against Orientia tsutsugamushi, mechanistic studies have been neglected. Valid animal models will enable experiments to elucidate protective and pathologic immune mechanisms. The public health need for vaccines against these agents of human disease, most clearly O. tsutsugamushi, and the veterinary diseases, canine monocytotropic ehrlichiosis (E. canis), heartwater (E. ruminantium) and bovine anaplasmosis (A. marginale) requires detailed immunity and immunopathology investigations, including the roles of CD8 T lymphocytes.

Canine vector-borne pathogens in rural dogs in Chile: molecular survey and co-infection patterns

“…It is close to the prevalences reported by Brown et al [69] in free-roaming dogs associated with remote Aboriginal communities in Australia, but higher than other studies carried out in Brazil [62], Ivory Coast [70], Kenya [70] and Uganda [59]. The higher probability of A. platys infections in young dogs in our study was already been recorded in a previous study in Africa [70], most likely due to a primary exposure of juvenile individuals to the pathogen [71,72] and might be related to the lower levels CD8 T lymphocytes found in young dogs [73], which has a role in clearance of rickettsial infections [74]. In agreement with our results, other studies found that dogs infested with R. sanguineus were more likely to be infected with or exposed to Anaplasma spp.…”

Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos

“…If the cellular tropism of R . typhi and the associated cytotoxic T cell responses providing protective immunity in part by cytotoxicity towards infected cells contribute to nucleosome release remains to be determined [ 8 , 46 ]. However, in scrub typhus the data point towards neutrophils as a potential source of nucleosomes, contributing to disease exacerbation reflected by association to clinical disease severity ( Table 2 ).…”

Strong interferon-gamma mediated cellular immunity to scrub typhus demonstrated using a novel whole cell antigen ELISpot assay in rhesus macaques and humans

“…tsutsugamushi infected monocyte-derived dendritic cells induce production of IFN-γ from CD4+ T-cells [ 17 ]. Scrub typhus is universally fatal in CD8-deficient mice (compared to 50% fatality in wild type mice) [ 18 ], and CD8+ T-cells play a vital protective role in control of O . tsutsugamushi growth [ 19 ].…”