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.