Abstract
Ehrlichia chaffeensis is an obligate intracellular bacterium belonging to the order, Rickettsiales and is a frequent cause of severe and fatal tick-borne infection in people in North America. The reservoir host for E. chaffeensis is the white-tailed deer, while humans and dogs are regarded as common incidental hosts. In dogs, we and others have shown that E. chaffeensis establishes a chronic infection that persists for several weeks to months, while promoting the development of Th1 and Th17 cellular responses and pathogen-specific humoral immunity. We demonstrate here that vaccination with a live, attenuated clone of E. chaffeensis bearing a targeted mutation in the Ech_0230 gene neither promotes the development of long-lived cellular or humoral immunity, nor confers protection against secondary wild-type E. chaffeensis challenge. In dogs, a population of mature CD4+CD8+ double-positive (DP) T cells exists in the periphery that shares similarities with the DP T cell populations that have been described in humans and swine. Little is known about the function of these cells, particularly in the context of infectious diseases. Here, we demonstrate that canine DP T cells expand significantly in response to E. chaffeensis infection. Using in vitro antigen recall assays, we further demonstrate that canine DP T cells undergo clonal expansion, produce IFNγ and IL-17, and upregulate expression of granzyme B and granulysin. Together, our results demonstrate that DP T cells accumulate in the host during E. chaffeensis infection, and suggest that alternative lymphocyte populations may participate in the immune response to tick-borne infections in the incidental host.
Highlights
Ehrlichia chaffeensis is a Gram-negative, obligate intracellular bacterium
One of these mutant clones, containing a transposon insertion in the Ech_0660 gene, was found to induce a strong immune response in white-tailed deer and dogs, and we recently reported that vaccination with the live, attenuated Ech_0660 mutant organisms conferred protection from both needle- and tick-transmitted wild-type E. chaffeensis infection in dogs [9, 10]
All animals were negative for ehrlichemia at all time points (Table 1), indicating that the targeted mutant organism was rapidly cleared, and suggesting that the Ech_0230 gene may be required to establish a productive E. chaffeensis infection in the mammalian host
Summary
Ehrlichia chaffeensis is a Gram-negative, obligate intracellular bacterium. It is a member of the order Rickettsiales, in the family Anaplasmataceae. It is the causative agent of human monocytic ehrlichiosis (HME) [1,2,3]. HME causes significant morbidity, with 40–60% of reported cases requiring hospitalization, and mortality in 3–5% of infected individuals [4, 5]. DP T Cells and Immunity to E. chaffeensis Infection are frequently attributed to delays in diagnosis and treatment, as well as infection in children and immunocompromised individuals [6]. Treatment options for E. chaffeensis infection are limited to a single class of tetracycline antibiotics, and there is no approved vaccine for use in humans or animals
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