Research Papers: Immunology:
Antigen specific immune response in Chlamydia muridarum genital infection is dependent on murine microRNAs-155 and -182
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Rishein Gupta1,*, Tanvi Arkatkar1,*, Jonathon Keck1, Gopala Krishna Lanka Koundinya1, Kevin Castillo1, Sabrina Hobel2, James P. Chambers1, Jieh-Juen Yu1, M. Neal Guentzel1, Achim Aigner2, Lane K. Christenson3 and Bernard P. Arulanandam1
1 South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA
2 Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Härtelstraße, Leipzig, Germany
3 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA
* These authors have contributed equally to this work
Bernard P. Arulanandam, email:
Keywords: Chlamydia muridarum, host immunity, microRNA-155, microRNA-182, CD4+ T-cells, Immunology and Microbiology Section, Immune response, Immunity
Received: July 22, 2016 Accepted: August 02, 2016 Published: August 20, 2016
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.
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