Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host

• Published in: PloS one Vol. 11; no. 2; p. e0148229
• Main Authors: McGill, Jodi L, Nair, Arathy D S, Cheng, Chuanmin, Rusk, Rachel A, Jaworski, Deborah C, Ganta, Roman R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.02.2016; Public Library of Science (PLoS)
• Subjects: Anaplasma phagocytophilum; Animals; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Arachnids; Attenuation; Biology and Life Sciences; Blood; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Chlamydia; Deer; Dogs; Ehrlichia; Ehrlichia canis; Ehrlichia chaffeensis; Ehrlichia chaffeensis - genetics; Ehrlichia chaffeensis - immunology; Ehrlichiosis; Ehrlichiosis - immunology; Ehrlichiosis - microbiology; Ehrlichiosis - prevention & control; Ehrlichiosis - veterinary; Helper cells; Immune response; Immune response (humoral); Immune system; Immunity; Infections; Insect Vectors - microbiology; Interferon-gamma - biosynthesis; Interleukin 17; Interleukin-17 - biosynthesis; Intravenous administration; Leukocytes; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Monocytes; Mutation; Pathogens; Peripheral blood; Rickettsial Vaccines - immunology; Ticks - microbiology; Vaccination; Vaccination - veterinary; Vaccines; Vaccines, Attenuated - immunology; Vectors (Biology); Veterinary colleges; Veterinary medicine; γ-Interferon; United States > US; Kansas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148229

Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous-administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild-type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4+ T cell proliferation and IFNγ production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection.