title: Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis.
abstract: MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity.
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Lochhead
authors.affiliation: Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: Zachary
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Dalla Rosa
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Weis
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Janis J
authors.initials: JJ
authors.lastname: Weis
mesh_terms: D000818:Animals; D001168:Arthritis / Q000378:metabolism* / Q000382:microbiology; D001854:Bone Marrow Cells / Q000166:cytology; D025065:Borrelia burgdorferi; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D007107:Immune System; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000378:metabolism*; D008193:Lyme Disease / Q000378:metabolism* / Q000382:microbiology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D009205:Myocarditis / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis; D011485:Protein Binding; D018417:Th1 Cells / Q000166:cytology
chemical_list: C556062:IL10 protein, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016753:Interleukin-10