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.
Highlights
Innate and adaptive immune cells originate from hematopoietic stem cells (HSCs)
Five-weeks-old mice were immunized with phosphate buffered saline (PBS), acellular vaccines (ACVs), or whole cell vaccines (WCVs) (Table S1), boosted, and subsequently challenged with Bordetella pertussis (Bp)
Our WCVimmunized mice exhibit increases in white blood cells at day 3 post-immunization when compared to PBS and ACVimmunized mice
Summary
Innate and adaptive immune cells originate from hematopoietic stem cells (HSCs). Hematopoietic stem and progenitor cell (HSPC) renewal, expansion, and differentiation are tightly regulated to produce and maintain sufficient blood cells [2]. Cell–cell interactions, microenvironment contributions, cytokines, and gene signature changes prompt HSPC expansion [1, 3]. During infection, this results from: [1] direct pathogen interaction or signals that push differentiation and/or mobilization or [2] a pull to replenish leukocytes required for immune surveillance and clearing infection [4, 5]. Long-term immunity is maintained by antigen-specific memory B and T cells. Recent evidence suggests that innate immune cells provide long-term immunity independently [7,8,9]
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