title: Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens.
abstract: Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of Salmonella infection on erythroid development and found that systemic infection induced anemia, splenomegaly, elevated erythropoietin (EPO) levels, and extramedullary erythropoiesis in a process independent of Salmonella pathogenicity island 2 (SPI2) or flagellin. The circulating EPO level was also constitutively higher in mice lacking the expression of signal-regulatory protein α (SIRPα). The expression level of EPO mRNA was elevated in the kidney and liver but not increased in the spleens of infected mice despite the presence of extramedullary erythropoiesis in this tissue. In contrast to data from a previous report, mice lacking EPO receptor (EPOR) expression on nonerythroid cells (EPOR rescued) had bacterial loads similar to those of wild-type mice following Salmonella infection. Indeed, treatment to reduce splenic erythroblasts and mature red blood cells correlated with elevated bacterial burdens, implying that extramedullary erythropoiesis benefits the host. Together, these findings emphasize the profound effect of Salmonella infection on erythroid development and suggest that the modulation of erythroid development has both positive and negative consequences for host immunity.
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Lin-Xi
authors.initials: LX
authors.lastname: Li
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Benoun
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA Department of Molecular and Cellular Physiology and Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Kipp
authors.initials: K
authors.lastname: Weiskopf
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA Department of Molecular and Cellular Physiology and Department of Structural Biology, Stanford University School of Medicine, Stanford, California, USA Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: K Christopher
authors.initials: KC
authors.lastname: Garcia
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA sjmcsorley@ucdavis.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McSorley
mesh_terms: D000740:Anemia / Q000097:blood; D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000378:metabolism*; D005434:Flow Cytometry; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012480:Salmonella Infections / Q000378:metabolism* / Q000382:microbiology*; D012485:Salmonella typhi; D013154:Spleen / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D011971:Receptors, Immunologic; D004921:Erythropoietin