Antigen specific immune response in Chlamydia muridarum genital infection is dependent on murine microRNAs-155 and-182

作者：Gupta Rishein; Arkatkar Tanvi; Keck Jonathon; Koundinya Gopala Krishna Lanka; Castillo Kevin; Hobel Sabrina; Chambers James P; Yu Jieh Juen; Guentzel M Neal; Aigner Achim; Christenson Lane K; Arulanandam Bernard P

来源：Oncotarget, 2016, 7(40): 64726-64742.

DOI：10.18632/oncotarget.11461

• Chlamydia muridarum
• host immunity
• microRNA-155
• microRNA-182
• dendritic cells
• CD4(+) T-cells
• Immunology and Microbiology Section
• Immune response
• Immunity

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-gamma 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-gamma 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.

• 出版日期2016-10-4