Reinfection with Anaplasma phagocytophilum in BALB/c mice and cross-protection between two sympatric isolates

Abstract

Infection with Anaplasma phagocytophilum in white-footed mice results in partial protection against reinfection with the same agent. However, humans and domestic animals may be sequentially exposed to different isolates of the agent circulating in the same or adjacent foci. We investigated whether immune response to a tick-borne infection with A. phagocytophilum provides protection against homologous and heterologous challenges. BALB/c mice were infected with one of the two sympatric isolates of A. phagocytophilum via tick bite and challenged 16 weeks later by Ixodes scapularis nymphs infected with either the same or the alternative isolate. As controls, groups of infected mice were challenged by uninfected ticks to confirm an absence of reactivation of the original infection or groups of naive mice were fed upon by ticks from cohorts used for an infectious challenge. Xenodiagnostic I. scapularis larvae were fed upon each mouse at 14 and 21 days postchallenge (PCH) and tested for the presence of A. phagocytophilum as freshly molted nymphs. Blood samples for quantitative PCR were collected at 7, 14, 21, and 70 days PCH. Serum samples were collected weekly to monitor development of immune response. The proportion of infected animals, levels of bacteremia, and the prevalence of infection in xenodiagnostic ticks were higher in groups of control mice exposed to A. phagocytophilum for the first time than in mice reinfected with either homologous or heterologous isolates. The presence of antibodies against A. phagocytophilum did not protect mice from a challenge with either homologous or heterologous isolates, however the ensuing reinfection was significantly milder and of a shorter duration than the first infection with either isolate.

FIG. 1.

Scheme of the experiment for groups of mice with primary infection with A. phagocytophilum Dawson isolate. Group I, control without an infectious challenge; group II, mice subjected to a homologous challenge; group III, mice subjected to a heterologous challenge; group IV, control without the primary infection. Four similar groups of mice were designated for primary infection with A. phagocytophilum Gaillard isolate.

FIG. 2.

Dynamics of antibody titers in BALB/c mice originally infected with A. phagocytophilum Dawson isolate and challenged with homologous or heterologous isolates. Group 1, unchallenged control; group 2, homologous challenge (Dawson-Dawson); group 3, heterologous challenge (Dawson-Gaillard); group 4, pathogen-naive control. The vertical line indicates placement of challenging ticks. Error bars show standard deviations.

FIG. 3.

Dynamics of antibody titers in BALB/c mice originally infected with A. phagocytophilum Gaillard isolate and challenged with homologous or heterologous isolates. Group 5, unchallenged control; group 6, homologous challenge (Gaillard-Gaillard); group 7, heterologous challenge (Gaillard-Dawson); group 8, pathogen-naive control. The vertical line indicates placement of challenging ticks. Error bars show standard deviations.