Genetic background influences the NK recruitment and Th1 polarization in response to TLR agonists (VAC3P.955)

Abstract

In response to vaccines, DCs do not act in isolation but potentiate their efficiency by interacting with NK cells. The recognition of PAMPs by TLRs triggers DC maturation which is essential for their migration and T-cell priming. Maturing DCs release IL-12 which regulates the function of NK cells and drives the Th1 cells differentiation. In turn, NK cells which are activated by IL-12 and PAMPs through their own TLRs, provide IFN-γ necessary for enhancing stable IL-12 production by DCs and maintaining Th1 cell polarization. Studies using Balb/c strain showed that TLR agonist R848 induces NK cell recruitment into lymph nodes and augments Th1 polarization through unknown mechanisms. In this study we tested whether the genetic background will influence the NK cell recruitment and subsequent Th1 polarization in response to vaccine formulated with a panel of TLR agonists and alhydrogel. We found that immunization with OVA protein mixed with TLR agonist R848 among adjuvants tested, increased up to 3-fold recruitment of IFN-γ producing CD27+CD11b+ NK cell expressing CXCR3 and CD62L in lymph nodes and spleen of Balb/c but to a much lesser extent in B6 mice. Interestingly, however, the increased in NK cell recruitment had limited impact on Th1 polarization in Balb/c as compared to Th1-prone B6 mice. These data suggest that for optimal Th1 polarization, adjuvant or adjuvant combination should be selected based on their ability to both recruit and maximize DC-NK bidirectional signaling.