Author ORCID Identifier
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https://orcid.org/0000-0002-5329-1927
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https://orcid.org/0000-0003-1583-2056
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https://orcid.org/0000-0002-3250-3636
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Document Type
Article
Publication Date
2018
College/Unit
School of Medicine
Department/Program/Center
Microbiology, Immunology, and Cell Biology
Abstract
Hematopoietic stem and progenitor cell (HSPC) compartments are altered to direct immune responses to infection. Their roles during immunization are not well-described. To elucidate mechanisms for waning immunity following immunization with acellular vaccines (ACVs) against Bordetella pertussis (Bp), we tested the hypothesis that immunization with Bp ACVs and whole cell vaccines (WCVs) differ in directing the HSPC characteristics and immune cell development patterns that ultimately contribute to the types and quantities of cells produced to fight infection. Our data demonstrate that compared to control and ACV-immunized CD-1 mice, immunization with an efficacious WCV drives expansion of hematopoietic multipotent progenitor cells (MPPs), increases circulating white blood cells (WBCs), and alters the size and composition of lymphoid organs. In addition to MPPs, common lymphoid progenitor (CLP) proportions increase in the bone marrow of WCV-immunized mice, while B220+ cell proportions decrease. Upon subsequent infection, increases in maturing B cell populations are striking in WCV-immunized mice. RNAseq analyses of HSPCs revealed that WCV and ACV-immunized mice vastly differ in developing VDJ gene segment diversity. Moreover, gene set enrichment analyses demonstrate WCV-immunized mice exhibit unique gene signatures that suggest roles for interferon (IFN) induced gene expression. Also observed in naïve infection, these IFN stimulated gene (ISG) signatures point toward roles in cell survival, cell cycle, autophagy, and antigen processing and presentation. Taken together, these findings underscore the impact of vaccine antigen and adjuvant content on skewing and/or priming HSPC populations for immune response.
Digital Commons Citation
Varney, Melinda E.; Boehm, Dylan T.; DeRoos, Katherine; Nowak, Evan S.; Wong, Ting Y.; Sen-Kilic, Emel; Bradford, Shebly D.; Elkins, Cody; Epperly, Matthew S.; Witt, William T.; Barbier, Mariette; and Damron, F. Heath, "Bordetella pertussis Whole Cell Immunization, Unlike Acellular Immunization, Mimics Naïve Infection by Driving Hematopoietic Stem and Progenitor Cell Expansion in Mice" (2018). Faculty & Staff Scholarship. 1328.
https://researchrepository.wvu.edu/faculty_publications/1328
Source Citation
Varney ME, Boehm DT, DeRoos K, Nowak ES, Wong TY, Sen-Kilic E, Bradford SD, Elkins C, Epperly MS, Witt WT, Barbier M and Damron FH (2018) Bordetella pertussis Whole Cell Immunization, Unlike Acellular Immunization, Mimics Naïve Infection by Driving Hematopoietic Stem and Progenitor Cell Expansion in Mice. Front. Immunol. 9:2376. https://doi.org/10.3389/fimmu.2018.02376
Comments
Copyright © 2018 Varney, Boehm, DeRoos, Nowak, Wong, Sen-Kilic, Bradford, Elkins, Epperly, Witt, Barbier and Damron. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.