Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (Anaplasmataceae)

The family Anaplasmataceae includes several species of obligate intracellular gram-negative bacteria. The early immune responses to Ehrlichia and Anaplasma infections are likely to be important factors in determining the outcome of infection and clinical course of disease. This chapter discusses recent studies on the kinetics and quality of early immune responses to Ehrlichia and briefly to Anaplasma, and the implications for development of successful preventative immune-based therapeutic approaches. Five Anaplasmataceae members can infect humans, but only two of them—Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME); and Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis (HGA)—have been thoroughly investigated. There is only limited information on the mechanisms of pathogenesis of Ehrlichia and Anaplasma and the role of host innate immune responses in contributing to disease virulence in humans; therefore, animal models are necessary to identify bacterial and host characteristics of disease. Murine models have been developed to studydifferences in host immunity and disease susceptibility. E.muris-infected DCs from MyD88—/— mice are able to stimulate gamma interferon (IFN-ү); production by innate invariant natural killer T (iNKT) lymphocytes. Such responses were dependent on direct recognition of unidentified ehrlichial ligands by CD1d, but were not dependent on TLR signals. The author has investigated the contribution of NK cells to protective immunity against Ehrlichia. Studies of the pathogenesis of severe and fatal ehrlichiosis and anaplasmosis, or protective immunity against Ehrlichia and Anaplasma infection, have largely focused on the analysis of effector CD4+ T cells and their control by CD8+ T cells.