Transcriptome signature for dampened Th2 dominance in acellular pertussis vaccine-induced CD4+ T cell responses through TLR4 ligation

Abstract

Current acellular pertussis (aP) vaccines promote a T helper 2 (Th2)-dominated response, while Th1/Th17 cells are protective. As our previous study showed, after adding a non-toxic TLR4 ligand, LpxL1, to the aP vaccine in mice, the Bordetella pertussis-specific Th2 response is decreased and Th1/Th17 responses are increased as measured at the cytokine protein level. However, how this shift in Th response by LpxL1 addition is regulated at the gene expression level remains unclear. Transcriptomics analysis was performed on purified CD4 + T cells of control and vaccinated mice after in vitro restimulation with aP vaccine antigens. Multiple key factors in Th differentiation, including transcription factors, cytokines, and receptors, were identified within the differentially expressed genes. Upregulation of Th2-and downregulation of follicular helper T cell-associated genes were found in the CD4 + T cells of both aP-and aP+LpxL1-vaccinated mice. Genes exclusively upregulated in CD4 + T cells of aP+LpxL1-vaccinated mice included Th1 and Th17 signature cytokine genes Ifng and Il17a respectively. Overall, our study indicates that after addition of LpxL1 to the aP vaccine the Th2 component is not downregulated at the gene expression level. Rather an increase in expression of Th1-and Th17-associated genes caused the shift in Th subset outcome. Pertussis or whooping cough, caused by the gram-negative bacterium Bordetella pertussis, remains endemic even in highly vaccinated populations