A comparative study on the mechanisms of innate immune responses in mice induced by Alum and Actinidia eriantha polysaccharide

Abstract

The innate immune mechanisms by which adjuvants enhance the potency and protection of vaccine remain at cellular level, but the molecular mechanisms, especially in vivo, are ill-identified. Actinidia eriantha polysaccharide (AEPS) is a potent adjuvant with dual Th1 and Th2 potentiating activity, while Alum elicits a strict Th2 response. The current experiments were designed to compare the innate immune responses in the peritoneal cavity of mice induced by two adjuvants and explore their molecular mechanisms using gene expression microarray including long noncoding RNAs (lncRNAs). AEPS induced the recruitment of monocytes, neutrophils and dendritic cells. However, Alum recruited neutrophils and eosinophils. AEPS and Alum specifically induced the differential expression of 546 and 922 genes in peritoneal cells, respectively. AEPS induced higher mRNA expression of CCL2, CCL3, CCL4, CCL7, CXCL2, CXCL3, CXCL5, CXCL10, IL-12β, and IL-23α in immune effector process, while Alum tended to Th17 response mRNAs such as IL-7A, IL-17F and IL-17RA. Furthermore, a robust adjuvant-specific expression pattern of lncRNAs was found in above mentioned biological processes, suggesting the involvement of lncRNAs in immune responses induced by AEPS and Alum. This study led to a better understanding of different molecular mechanisms of adjuvants and benefited the rational design of effective vaccines.

Keywords: Actinidia eriantha; Alum; Innate immunity; Microarray; Polysaccharide; lncRNA.