title: Influence of Genetic Background on Hematologic and Histopathologic Alterations during Acute Granulocytic Anaplasmosis in 129/SvEv and C57BL/6J Mice Lacking Type I and Type II Interferon Signaling.
abstract: The role of host type I IFN signaling and its interaction with other immune pathways during bacterial infections is incompletely understood. Type II IFN signaling plays a key role during numerous bacterial infections including granulocytic anaplasmosis (GA) caused by Anaplasma phagocytophilum infection. The function of combined type I and type II IFN signaling and their potential synergism during GA and similar tick-borne diseases is a topic of current research investigation. The goal of this study was to evaluate 2 mouse models of absent type I/type II IFN signaling in experimental A. phagocytophilum infection to determine the effects of background strain. Mice lacking both type I and type II IFN receptor signaling (IFNAR-/-/IFNGR-/-) on either the 129/SvEv or C57BL/6J genetic background were evaluated at days 0, 6, 8, and 12 of infection. Pathogen burden in multiple organs was largely similar between strains of infected mice, with few significant differences. Background strain influenced the immune response to infection. Mice of the 129/SvEv strain developed more severe hematologic abnormalities, particularly more severe leukocytosis with marked neutrophilia and lymphocytosis, throughout acute infection. Histopathologic changes occurred in infected mice of both strains and varied in severity by organ. 129/SvEv mice developed more severe pathologic changes in spleen and bone marrow, whereas C57BL/6J mice developed more severe renal pathology. This work highlights the importance of mouse background strain in dictating pathophysiologic response to infection and informs future work regarding the loss of type I and type II IFN signaling on the immune response during GA.
authors.affiliation: Department of Biomedical Sciences, Oregon State University College of Veterinary Medicine, Corvallis, Oregon;, Email: jennifer.johns@oregonstate.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Johns
authors.affiliation: Departments of Comparative Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Marielle L
authors.initials: ML
authors.lastname: Discipulo
authors.affiliation: Departments of Pediatrics, Stanford University School of Medicine, Stanford, California.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Koehne
authors.affiliation: Departments of Comparative Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Kaitlin A
authors.initials: KA
authors.lastname: Moorhead
authors.affiliation: Departments of Comparative Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Claude M
authors.initials: CM
authors.lastname: Nagamine
mesh_terms: D000712:Anaplasmosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D059208:Parasite Load; D015398:Signal Transduction / Q000235:genetics
chemical_list: D007370:Interferon Type I; D007371:Interferon-gamma