Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils and causes human anaplasmosis (formerly human granulocytic ehrlichiosis). Interferon (IFN)-γ causes immunopathology in A. phagocytophilum infection models. Plasma IFN-γ levels are elevated 4 h after infection in experimentally infected mice, which indicates innate immunity and possible Toll-like receptors (TLRs). The ability of A. phagocytophilum to trigger proinflammatory responses via nuclear factor (NF)-κB was tested in TLR2-and TLR4-transfected cell lines and in primary murine macro-phages devoid of TLR2 or TLR4. NF-κB was activated only through TLR2, which suggests its role in innate immune induction with A. phagocytophilum infections. The role of innate immunity in human anaplasmosis immunopathology requires more study.