Selected TLR Agonists Act in Synergy to Reprogram DC-NK Cross-talk and Generate Effector T cells in Nicotinic Environment

The magnitude of immune responses to vaccination
is a critical factor in determining protection from diseases.
We reported that nicotine disrupts the properties
of DCs that are pivotal in the initiation of immune
response to vaccines. Here we investigated whether
TLR agonist(s) could overcome the effects of nicotine
on human DC and DC-NK cross-talk essential
for effector T cell generation. nicDC, nicDC-NK, and
nicDC-NK-T cultures exposed to TLR agonists were
evaluated for expression of costimulatory molecules,
cytokines, and intracellular cytokine IFN-g using ELISA
and flow cytometry. Our data shows that among
the TLR agonists, TLR3 and TLR8/7 synergistically
optimized nicDC maturation co-cultured NK cell activation.
Importantly, similar to DC-NK, nicDC-NK treated
with TLR3 and TLR8/7 and co-cultured with naïve
T cells promoted a comparable number of effector T
cells. Our data suggest that the addition of appropriate
TLR agonist(s) to vaccine formulation could potentially
improve the smokers’ immune response to
vaccination.