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

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is expected to be the third leading cause of death, and the fifth leading cause of disability by 2020 [29] . The Global Initiative for Chronic Obstructive Lung Disease defines COPD as characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations are associated with increased airway and systemic inflammation, and evidence suggests that 70% may be caused by microorganisms [30] . Two pathogens that are associated with acute exacerbations and the progression of COPD are the CEACAM-interacting pathogens M. catarrhalis and H. influenzae, which often colonize the mucosa of the lower human respiratory tract in patients with COPD [31] [32] [33] . M. catarrhalis and H. influenzae express structurally unrelated outer membrane proteins, ubiquitous surface protein A1 (UspA1), and P5homologous adhesin (P5), respectively, that share the ability to bind to the extracellular immunoglobulin V (IgV)like domain of human CEACAM1 [5, 8] . The interaction of CEACAM1 with M. catarrhalis results in reduced TLR2-initiated inflammatory responses of primary pulmonary epithelial cells [16] . CEACAM5 and CEACAM6 can mediate bacterial adhesion as well [5, 7, 8, 34] . All three CEACAMs in human airway epithelia can therefore be of importance for the colonization of the lower airways and have a role in acute exacerbations. Since the lower respiratory airways are normally sterile and protected by mucociliary clearance, CEACAMs expressed here are most likely to encounter bacteria in medical conditions leading to dysfunction of the mucociliary clearance, such as COPD [35] . To date, a comprehensive analysis of (co-) expression patterns of CEACAM1 isoforms, CEACAM5 and CEACAM6 in the different lung tissues is lacking.