Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons

Klaile, Esther; Klassert, Tilman E; Scheffrahn, Inka; Müller, Mario M; Heinrich, Annina; Heyl, Kerstin A; Dienemann, Hendrik; Grünewald, Christiane; Bals, Robert; Singer, Bernhard B; Slevogt, Hortense

Next, the effects of acute NTHi and Moraxella catarrhalis infection on CEACAM1, CEACAM5 and CEACAM6 mRNA expression levels in NHBE cells were investigated ( Figure 5 ). qPCR analysis revealed no differences in CEACAM5 and CEACAM6 expression upon bacterial infection. The M. catarrhalis wild type strains 25238 and BBH18 as well as the NTHi wild type strains 2019 and 1128 enhanced the mRNA expression of all four transmembrane CEACAM1-isoforms to a similar degree in a co-regulatory manner ( Figure 5A,B,D,E) . The mean induction of CEACAM1 transcription by M. catarrhalis strains was twice as high as by NTHi strains (3.5-5.5 fold vs. 1.9-2.8 fold). Since all four pathogens can bind to CEACAM1, we next tested whether this interaction was essential to the up-regulation of CEACAM1. To that end we used the M. catarrhalis UspA deletion mutant BBH18.1 and the NTHi P5 deletion mutant 1128f-, which both lack the respective CEACAM1-binding adhesin ( Figure 5C,F) . Again, the infection with these strains induced an elevated CEACAM1 expression (4.0-4.9 fold and 1.9-2.4 fold, respectively) comparable to their parental strains, indicating a CEACAM1-independent, more general mechanism for this effect. We then tested whether the CEACAM1 upregulation might be due to an increase in interferons. Both