Chlamydia Infection-derived Exosomes Possess Immunomodulatory Properties Capable of Stimulating Dendritic Cell Maturation
Raedeen S. Russell
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Khamia Ryans
Department of Biology, Clark Atlanta University, Atlanta, GA, USA.
Ming Bo Huang
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Yusuf Omosun
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Mahfuz Khan
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Michael D. Powell
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Joseph U. Igietseme
National Center for Emerging Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
Francis O. Eko
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA
*Author to whom correspondence should be addressed.
Abstract
Aims: The aim of this study was to characterize exosomes derived from Chlamydia muridarum-infected and normal healthy untreated mouse oviduct epithelial cells (MOEC) and evaluate their immunomodulatory properties.
Methodology: Exosomes were purified from C. muridarum-infected and uninfected MOEC and analyzed using the NanoSight nanoparticle tracking analysis system. The concentration of cytokines and chemokines associated with exosomes and secreted by exosome-activated bone marrow-derived dendritic cells (BMDCs) was assessed using the Bio-Plex cytokine assay kit in combination with the Bio-Plex Manager software. Also, the exosome-stimulated dendritic cell expression of co-stimulatory surface and major histocompatibility complex class II (MHC-II) molecules was assessed by FACS analysis.
Results: The results showed that the concentration of cytokines (IL-6, IL-10, IL-12, IFN-γ and TNF-α) and chemokines (KC (CXCL1), MCP-1 (CCL2), MIP-1α (CCL3), Rantes (CCL5) and Eotaxin (CCL11)) secreted by BMDCs pulsed with Chlamydia infection-derived exosomes (IDEX) was significantly higher (p < 0.05) than that secreted by BMDCs pulsed with uninfected control-derived exosomes (CDEX). Furthermore, exosomes purified from Chlamydia-infected MOEC significantly upregulated (p < 0.05) the dendritic cell expression of CD86 and MHC-II, molecules associated with DC activation and maturation, compared to those from uninfected cells.
Conclusion: The results indicate that Chlamydia IDEX possess immunomodulatory properties capable of stimulating dendritic cell activation and maturation. Further studies will delineate their potential use as immunomodulators or as vaccine delivery vehicles.
Keywords: Exosomes, Chlamydia, infection, proinflammatory cytokines, immunomodulation