MicroRNA155 Plays a Critical Role in the Pathogenesis of Cutaneous Leishmania major Infection by Promoting a Th2 Response and Attenuating Dendritic Cell Activity.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0370502 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-2191 (Electronic) Linking ISSN: 00029440 NLM ISO Abbreviation: Am J Pathol Subsets: MEDLINE
    • Publication Information:
      Publication: 2011-: New York : Elsevier
      Original Publication: Philadelphia [etc.] American Assn. of Pathologists [etc.]
    • Subject Terms:
      Cytokines/*immunology ; Leishmania major/*immunology ; Leishmaniasis, Cutaneous/*immunology ; MicroRNAs/*genetics; Animals ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/immunology ; Female ; Killer Cells, Natural/immunology ; Leishmania major/pathogenicity ; Leishmaniasis, Cutaneous/parasitology ; Mice ; Mice, Inbred C57BL ; Th2 Cells/immunology
    • Abstract:
      Interferon (IFN)-γ is indispensable in the resolution of cutaneous leishmaniasis (CL), while the Th2 cytokines IL-4, IL-10, and IL-13 mediate susceptibility. A recent study found that miR155, which promotes CD4 + Th1 response and IFN-γ production, is dispensable in the control of Leishmania donovani infection. Here, the role of miR155 in CL caused by L. major was investigated using miR155-deficient (miR155 -/- ) mice. Infection was controlled significantly quicker in the miR155 -/- mice than in their wild-type (WT) counterparts, indicating that miR155 contributes to the pathogenesis of CL. Faster resolution of infection in miR155 -/- mice was associated with increased levels of Th1-associated IL-12 and IFN-γ and reduced production of Th2- associated IL-4, IL-10, and IL-13. Concentrations of IFN-γ + CD8 + T cells and natural killer cells in draining lymph nodes were significantly higher in the L. major-infected miR155 -/- mice than in the infected WT mice, as indicated by flow-cytometry. After in vitro IFN-γ stimulation, nitric oxide and IL-12 production were increased, IL-10 production was decreased, and parasite clearance was enhanced in L. major-infected miR155 -/- DCs compared to those in WT DCs. Furthermore, IFN-γ production from activated miR155 -/- T cells was significantly enhanced in L. major-infected miR155 -/- DCs. Together, these findings demonstrate that miR155 promotes susceptibility to CL caused by L. major by promoting Th2 response and inhibiting DC function.
      (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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    • Grant Information:
      K01 CA207599 United States CA NCI NIH HHS; R21 AI138555 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Cytokines)
      0 (MicroRNAs)
      0 (Mirn155 microRNA, mouse)
    • Publication Date:
      Date Created: 20210204 Date Completed: 20210517 Latest Revision: 20220503
    • Publication Date:
      20221213
    • Accession Number:
      PMC8132173
    • Accession Number:
      10.1016/j.ajpath.2021.01.012
    • Accession Number:
      33539779