title: Antigen specific immune response in Chlamydia muridarum genital infection is dependent on murine microRNAs-155 and -182.
abstract: Anti-chlamydial immunity involves efficient presentation of antigens (Ag) to effector cells resulting in Ag-specific immune responses. There is limited information on inherent underlying mechanisms regulating these events. Previous studies from our laboratory have established that select microRNAs (miRs) function as molecular regulators of immunity in Chlamydia muridarum (Cm) genital infection. In this report, we investigated immune cell type-specific miRs, i.e. miR-155 and -182, and the role in Ag-specific immunity. We observed significant up-regulation of miR-155 in C57BL/6 bone marrow derived dendritic cells (BMDC), and miR-182 in splenic Ag-specific CD4+ T-cells. Using mimics and inhibitors, we determined that miR-155 contributed to BMDC activation following Cm infection. Co-cultures of miR-155 over-expressed in BMDC and miR-182 over-expressed in Ag-specific CD4+ T-cells, or miR-155-/- BMDC with miR-182 inhibitor treated Ag-specific CD4+ T-cells, resulted in IFN-γ production comparable to Ag-specific CD4+ T-cells isolated from Cm infected mice. Additionally, miR-182 was significantly up-regulated in intranasally vaccinated mice protected against Cm infection. In vivo depletion of miR-182 resulted in reduction in Ag-specific IFN-γ and genital pathology in Cm infected mice. To the best of our knowledge, this is the first study to report an interaction of miR-155 (in Cm infected DC) and miR-182 (in CD4+ T-cell) resulting in Ag specific immune responses against genital Cm.
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Rishein
authors.initials: R
authors.lastname: Gupta
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Arkatkar
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Keck
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Gopala Krishna Lanka
authors.initials: GK
authors.lastname: Koundinya
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Castillo
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Härtelstraße, Leipzig, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hobel
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Härtelstraße, Leipzig, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D005835:Genitalia / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D034741:RNA, Small Interfering; D007371:Interferon-gamma
keywords: CD4+ T-cells; Chlamydia muridarum; Immune response; Immunity; Immunology and Microbiology Section; dendritic cells; host immunity; microRNA-155; microRNA-182