Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis.
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...
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Public Library of Science (PLoS)
2010-02-01
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| author | Diane E Brown Melissa W McCoy M Carolina Pilonieta Rebecca N Nix Corrella S Detweiler |
| author_facet | Diane E Brown Melissa W McCoy M Carolina Pilonieta Rebecca N Nix Corrella S Detweiler |
| author_sort | Diane E Brown |
| collection | DOAJ |
| description | 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 in live animals. Whereby secondary HLH is known to occur in human patients with typhoid fever and other infectious diseases, our characterization of a viable natural disease model of secondary HLH offers an important means to elucidate pathogenesis of poorly understood mechanisms of secondary HLH and investigation of novel therapies. We characterize previously unreported secondary HLH in a chronic mouse model of typhoid fever, and novel changes in hematology including decreased tissue ferric iron storage that differs from classically described anemia of chronic disease. Our studies demonstrate S. Typhimurium infection of mice is a natural infectious disease model of secondary HLH that may have utility for elucidating disease pathogenesis and developing novel therapies. |
| format | Article |
| id | doaj-art-9e014ef583df4154a48d9cfabdf98b96 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9e014ef583df4154a48d9cfabdf98b962025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-02-0152e944110.1371/journal.pone.0009441Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis.Diane E BrownMelissa W McCoyM Carolina PilonietaRebecca N NixCorrella S DetweilerHemophagocytic 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 in live animals. Whereby secondary HLH is known to occur in human patients with typhoid fever and other infectious diseases, our characterization of a viable natural disease model of secondary HLH offers an important means to elucidate pathogenesis of poorly understood mechanisms of secondary HLH and investigation of novel therapies. We characterize previously unreported secondary HLH in a chronic mouse model of typhoid fever, and novel changes in hematology including decreased tissue ferric iron storage that differs from classically described anemia of chronic disease. Our studies demonstrate S. Typhimurium infection of mice is a natural infectious disease model of secondary HLH that may have utility for elucidating disease pathogenesis and developing novel therapies.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009441&type=printable |
| spellingShingle | Diane E Brown Melissa W McCoy M Carolina Pilonieta Rebecca N Nix Corrella S Detweiler Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. PLoS ONE |
| title | Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. |
| title_full | Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. |
| title_fullStr | Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. |
| title_full_unstemmed | Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. |
| title_short | Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. |
| title_sort | chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009441&type=printable |
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