hemophagocytic macrophages harbor salmonella enterica during persistent infectionhemophagocytic巨噬细胞港口在持续感染沙门氏菌.pdfVIP

Hemophagocytic Macrophages Harbor Salmonella enterica during Persistent Infection 1 1¤ 2,3 1* Rebecca N. Nix , Sarah E. Altschuler , Peter M. Henson , Corrella S. Detweiler 1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America, 2 Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, United States of America, 3 Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado, United States of America Salmonella enterica subspecies can establish persistent, systemic infections in mammals, including human typhoid fever. Persistent S. enterica disease is characterized by an initial acute infection that develops into an asymptomatic chronic infection. During both the acute and persistent stages, the bacteria generally reside within professional phagocytes, usually macrophages. It is unclear how salmonellae can survive within macrophages, cells that evolved, in part, to destroy pathogens. Evidence is presented that during the establishment of persistent murine infection, macrophages that contain S. enterica serotype Typhimurium are hemophagocytic. Hemophagocytic macrophages are characterized by the ingestion of non-apoptotic cells of the hematopoietic lineage and are a clinical marker of typhoid fever as well as certain other infectious and genetic diseases. Cell culture assays were developed to evaluate bacterial survival in hemophagocytic macrophages. S. Typhimurium preferentially replicated in macrophages that pre- phagocytosed viable cells, but the bacteria were killed in macrophages that pre-phagocytosed beads or dead cells. These data suggest that during persistent infe