Discussion
Here we found increased PD-L1 mRNA levels in total blood cells isolated
from pre-school asthmatic children with a virus-induced asthma
phenotype, lower FEV1% and with high CRP serum levels, indicating that
worse asthma, in the presence of infections in the airways, is
associated with induced PD-L1 mRNA expression. IFNβ, released by
PBMCs in preschool children with HRV infected airways was found to
correlate with improved lung function, both in control and asthmatic
children. However, although in control children IFNβ directly correlated
with PD-L1 mRNA expression, in asthmatic children this
correlation was lost in peripheral blood.
PDL1 has been associated with Hepatitis B infections{Wang, 2013 #46}.
In this case the use of anti PDL1 inhibitors were suggested to improve
natural Killer T cell function resulting in inhibition of virus
replication. This mechanism reminds that described also in lung cancer
where anti PDL1 antibody treatment results in ameliorated anti-tumour
immune responses {Friedrich, 2018 #56;Vahl, 2017 #69}. Here we found
that PDL1 mRNA was induced in association with higher levels of the
infection marker CRP in the periphery but not with RV in the airways. In
addition, PDL1 mRNA did not directly correlated with IFN-beta release in
the peripheral blood of asthmatic children, indicating a possible
therapeutical IFN-mediated therapy for these asthmatic children.
Further, we recently reported that these asthmatic children have
prevalent gram negative colonization in the airways which are associated
with induction of IFN-beta release in the airways in their nasal
pharyngeal fluid {Hentschke, 2017 #76;}. Thus it is possible that the
direct correlation found between CRP and PDL1 relate to the presence of
gram negative bacteria in the airways of these children.
Taken together these data reveal that the host respond to infection with
release of IFNβ in blood cells. The infectious agent then redirects this
response by upregulating PDL1 which inhibits the immune system. In
asthma there seems to be a therapeutical possibility to use Interferon
type one to improve lung function without inducing PDL1 thus keeping
activated anti-infection immune responses.