Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection

Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We h...

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Main Authors: Simone Howard, Shakyra Richardson, Ifeyinwa Benyeogor, Yusuf Omosun, Kamran Dye, Fnu Medhavi, Stephanie Lundy, Olayinka Adebayo, Joseph U. Igietseme, Francis O. Eko
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.625318/full
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author Simone Howard
Shakyra Richardson
Ifeyinwa Benyeogor
Yusuf Omosun
Kamran Dye
Fnu Medhavi
Stephanie Lundy
Olayinka Adebayo
Joseph U. Igietseme
Francis O. Eko
author_facet Simone Howard
Shakyra Richardson
Ifeyinwa Benyeogor
Yusuf Omosun
Kamran Dye
Fnu Medhavi
Stephanie Lundy
Olayinka Adebayo
Joseph U. Igietseme
Francis O. Eko
author_sort Simone Howard
collection DOAJ
description Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and p-values < 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.
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spelling doaj.art-0d205d0c9c09477fb8965dbaa242fbfd2022-12-21T18:15:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.625318625318Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial InfectionSimone Howard0Shakyra Richardson1Ifeyinwa Benyeogor2Yusuf Omosun3Kamran Dye4Fnu Medhavi5Stephanie Lundy6Olayinka Adebayo7Joseph U. Igietseme8Francis O. Eko9Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesDepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesWinship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United StatesDepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesDepartment of Chemistry, Morehouse College, Atlanta, GA, United StatesDepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesDepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesDepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesCenters for Disease Control and Prevention (CDC), Atlanta, GA, United StatesDepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United StatesVaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and p-values < 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.https://www.frontiersin.org/articles/10.3389/fimmu.2021.625318/fullChlamydiaimmunizationinfectionmicroRNAimmunitypathology
spellingShingle Simone Howard
Shakyra Richardson
Ifeyinwa Benyeogor
Yusuf Omosun
Kamran Dye
Fnu Medhavi
Stephanie Lundy
Olayinka Adebayo
Joseph U. Igietseme
Francis O. Eko
Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection
Frontiers in Immunology
Chlamydia
immunization
infection
microRNA
immunity
pathology
title Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection
title_full Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection
title_fullStr Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection
title_full_unstemmed Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection
title_short Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection
title_sort differential mirna profiles correlate with disparate immunity outcomes associated with vaccine immunization and chlamydial infection
topic Chlamydia
immunization
infection
microRNA
immunity
pathology
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.625318/full
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