Comparative Experimental Infection Study in Dogs with Ehrlichia canis, E. chaffeensis, Anaplasma platys and A. phagocytophilum

Citation: Nair, A. D. S., Cheng, C., Ganta, C. K., Sanderson, M. W., Alleman, A. R., Munderloh, U. G., & Ganta, R. R. (2016). Comparative Experimental Infection Study in Dogs with Ehrlichia canis, E. chaffeensis, Anaplasma platys and A. phagocytophilum. Plos One, 11(2), 21. doi:10.1371/journal.pone.0148239Dogs acquire infections with the Anaplasmataceae family pathogens, E. canis, E. chaffeensis, E. ewingii, A. platys and A. phagocytophilum mostly during summer months when ticks are actively feeding on animals. These pathogens are also identified as causing diseases in people. Despite the long history of tick-borne diseases in dogs, much remains to be defined pertaining to the clinical and pathological outcomes of infections with these pathogens. In the current study, we performed experimental infections in dogs with E. canis, E. chaffeensis, A. platys and A. phagocytophilum. Animals were monitored for 42 days to evaluate infection-specific clinical, hematological and pathological differences. All four pathogens caused systemic persistent infections detectible throughout the 6 weeks of infection assessment. Fever was frequently detected in animals infected with E. canis, E. chaffeensis, and A. platys, but not in dogs infected with A. phagocytophilum. Hematological differences were evident in all four infected groups, although significant overlap existed between the groups. A marked reduction in packed cell volume that correlated with reduced erythrocytes and hemoglobin was observed only in E. canis infected animals. A decline in platelet numbers was common with E. canis, A. platys and A. phagocytophilum infections. Histopathological lesions in lung, liver and spleen were observed in all four groups of infected dogs; infection with E. canis had the highest pathological scores, followed by E. chaffeensis, then A. platys and A. phagocytophilum. All four pathogens induced IgG responses starting on day 7 post infection, which was predominantly comprised of IgG2 subclass antibodies. This is the first detailed investigation comparing the infection progression and host responses in dogs after inoculation with four pathogens belonging to the Anaplasmataceae family. The study revealed a significant overlap in clinical, hematological and pathological changes resulting from the infections

image_1_Antigen-Specific CD4+CD8+ Double-Positive T Cells Are Increased in the Blood and Spleen During Ehrlichia chaffeensis Infection in the Canine Host.PDF

<p>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.</p

Comparative Experimental Infection Study in Dogs with Ehrlichia canis, E. chaffeensis, Anaplasma platys and A. phagocytophilum.

Dogs acquire infections with the Anaplasmataceae family pathogens, E. canis, E. chaffeensis, E. ewingii, A. platys and A. phagocytophilum mostly during summer months when ticks are actively feeding on animals. These pathogens are also identified as causing diseases in people. Despite the long history of tick-borne diseases in dogs, much remains to be defined pertaining to the clinical and pathological outcomes of infections with these pathogens. In the current study, we performed experimental infections in dogs with E. canis, E. chaffeensis, A. platys and A. phagocytophilum. Animals were monitored for 42 days to evaluate infection-specific clinical, hematological and pathological differences. All four pathogens caused systemic persistent infections detectible throughout the 6 weeks of infection assessment. Fever was frequently detected in animals infected with E. canis, E. chaffeensis, and A. platys, but not in dogs infected with A. phagocytophilum. Hematological differences were evident in all four infected groups, although significant overlap existed between the groups. A marked reduction in packed cell volume that correlated with reduced erythrocytes and hemoglobin was observed only in E. canis infected animals. A decline in platelet numbers was common with E. canis, A. platys and A. phagocytophilum infections. Histopathological lesions in lung, liver and spleen were observed in all four groups of infected dogs; infection with E. canis had the highest pathological scores, followed by E. chaffeensis, then A. platys and A. phagocytophilum. All four pathogens induced IgG responses starting on day 7 post infection, which was predominantly comprised of IgG2 subclass antibodies. This is the first detailed investigation comparing the infection progression and host responses in dogs after inoculation with four pathogens belonging to the Anaplasmataceae family. The study revealed a significant overlap in clinical, hematological and pathological changes resulting from the infections

Impact of infections on platelet counts.

<p>The platelet counts in dogs infected with <i>E</i>. <i>chaffeensis</i>, <i>E</i>. <i>canis</i>, <i>A</i>. <i>platys</i> and <i>A</i>. <i>phagocytophilum</i> were compared with the values observed for uninfected controls. The values are shown as mean ± SD per group. Significant differences (<i>P</i> ≤ 0.05) observed between controls (open circle) and infected groups (closed circle) are identified with asterisks.</p

Body temperature changes in dogs infected with <i>E</i>. <i>canis</i>, <i>E</i>. <i>chaffeensis</i>, <i>A</i>. <i>platys</i> or <i>A</i>. <i>phagocytophilum</i>.

<p>Body temperature changes in dogs infected with <i>E</i>. <i>canis</i>, <i>E</i>. <i>chaffeensis</i>, <i>A</i>. <i>platys</i> or <i>A</i>. <i>phagocytophilum</i>.</p