Faculty Collaboration Database

Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. PLoS One 2015;10(8):e0135142

Date

08/08/2015

Pubmed ID

26252010

Pubmed Central ID

PMC4529177

DOI

10.1371/journal.pone.0135142

Scopus ID

2-s2.0-84941978921 (requires institutional sign-in at Scopus site)   21 Citations

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.

Author List

Lochhead RB, Zachary JF, Dalla Rosa L, Ma Y, Weis JH, O'Connell RM, Weis JJ

Author

Robert Lochhead PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arthritis
Bone Marrow Cells
Borrelia burgdorferi
Disease Models, Animal
Female
Gene Expression Regulation
Genotype
Immune System
Immunity, Innate
Interleukin-10
Lyme Disease
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs
Myocarditis
Phagocytosis
Protein Binding
Th1 Cells