chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis慢性鼠伤寒是一种自然模型的二级hemophagocytic lymphohistiocytosis.pdfVIP

Chronic Murine Typhoid Fever Is a Natural Model of Secondary Hemophagocytic Lymphohistiocytosis 1,2 1 1 1¤ 1 Diane E. Brown *, Melissa W. McCoy , M. Carolina Pilonieta , Rebecca N. Nix , Corrella S. Detweiler * 1 Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America, 2 Paleontology Section, Museum of Natural History, University of Colorado, Boulder, Colorado, United States of America Abstract Hemophagocytic lymphohistiocytosis (HLH) is a hyper-inflammatory clinical syndrome associated with neoplastic disorders especially lymphoma, autoimmune conditions, and infectious agents including bacteria, viruses, protozoa and fungi. In both human and veterinary medicine, hemophagocytic histiocytic disorders are clinically important and frequently fatal. HLH in humans can be a primary (familial, autosomal recessive) or secondary (acquired) condition, with both types generally precipitated by an infectious agent. Previously, no mouse model for secondary HLH has been reported. Using Salmonella enterica serotype Typhimurium by oral gavage to mimic naturally-occurring infection in Sv129S6 mice, we characterized the clinical, hematologic and morphologic host responses to disease thereby describing an animal model with the clinico- pathologic features of secondary HLH as set forth by the Histiocyte Society: fever, splenomegaly, cytopenias (anemia, thrombocytopenia), hemophagocytosis in bone marrow and spleen, hyperferritinemia, and hypofibrinogenemia. Disease severity correlates with high splenic and hepatic bacterial load, and we show disease course can be monitored and tracked i