PersistentEhrlichia chaffeensisInfection Occurs in the Absence of Functional Major Histocompatibility Complex Class II Genes

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Abstract
Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsiaEhrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance toE. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis ofE. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functionaltlr4gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for ≥30 days. In the absence of MHC-II alleles,E. chaffeensisinfections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4+T cells, are critical for conferring resistance toE. chaffeensis.