Murine MicroRNA-214 regulates intracellular adhesion molecule (ICAM1) gene expression in genital Chlamydia muridarum infection

Tanvi Arkatkar, Rishein Gupta, Weidang Li, Jieh Juen Yu, Shradha Wali, M. Neal Guentzel, James P. Chambers, Lane K. Christenson, Bernard P. Arulanandam

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The hallmark of chlamydial infection is the development of upper genital pathology in the form of hydrosalpinx and oviduct and/or tubal dilatation. Although molecular events leading to genital tissue presentation and cellular architectural remodelling are unclear, early-stage host immune responses are believed to contribute to these long-term sequelae. Recently, we reported the contribution of selected infection-associated microRNAs (miRs) in the generation of host immunity at early-stage infection (day 6 after intravaginal Chlamydia muridarum challenge in C57BL/6 mice). In this report, we describe the contribution of an infection-associated microRNA, i.e. miR-214, to host immunity. Chlamydia muridarum infection in the C57BL/6 mouse genital tract significantly down-regulated miR-214 while up-regulating intracellular adhesion molecule 1 (ICAM1) gene expression. These in vivo observations were confirmed by establishing direct regulation of ICAM-1 by miR-214 in ex vivo genital cell cultures in the presence of miR-214 mimic and inhibitor. Because, ICAM-1 contributes to recruitment of neutrophils following infection, we also demonstrated that alteration of ICAM1 by miR-214 in interleukin-17A-deficient (IL-17A-/-) mice correlated with reduction of neutrophils infiltrating genital tissue at day 6 after challenge. Additionally, these early-stage events resulted in significantly decreased genital pathology in IL-17A-/- mice compared with C57BL/6 mice. This report provides evidence for early-stage regulation of ICAM1 by microRNAs, resulting in reduction of genital pathology associated with chlamydial infection.

Original languageEnglish (US)
Pages (from-to)534-542
Number of pages9
JournalImmunology
Volume145
Issue number4
DOIs
StatePublished - Aug 1 2015

Keywords

  • Chlamydia muridarum
  • Genital pathology
  • Host responses
  • Intracellular adhesion molecule-1
  • MicroRNA-214
  • Murine genital tract

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Arkatkar, T., Gupta, R., Li, W., Yu, J. J., Wali, S., Neal Guentzel, M., Chambers, J. P., Christenson, L. K., & Arulanandam, B. P. (2015). Murine MicroRNA-214 regulates intracellular adhesion molecule (ICAM1) gene expression in genital Chlamydia muridarum infection. Immunology, 145(4), 534-542. https://doi.org/10.1111/imm.12470