Adaptive immunity to Anaplasma pathogens and immune dysregulation: Implications for bacterial persistence

Anaplasma marginale is an obligate intraerythrocytic bacterium that infects ruminants, and notably causes severe economic losses in cattle worldwide. Anaplasma phagocytophilum infects neutrophils and causes disease in many mammals, including ruminants, dogs, cats, horses, and humans. Both bacteria cause persistent infection - infected cattle never clear A. marginale and A. phagocytophilum can also cause persistent infection in ruminants and other animals for several years. This review describes correlates of the protective immune response to these two pathogens as well as subversion and dysregulation of the immune response following infection that likely contribute to long-term persistence. I also compare the immune dysfunction observed with intraerythrocytic A. marginale to that observed in other models of chronic infection resulting in high antigen loads, including malaria, a disease caused by another intraerythrocytic pathogen.