Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for <b><i>Moraxella catarrhalis</i></b>

Abstract

Moraxella catarrhalis is a Gram-negative human mucosal commensal and pathogen. It is a common cause of exacerbation in chronic obstructive pulmonary disease (COPD). During the process of infection, host colonization correlates with recognition of host molecular patterns. Importantly, in COPD patients with compromised epithelial integrity the underlying extracellular matrix is exposed and provides potential adhesive targets. Collagen VI is a ubiquitous fibrillar component in the airway mucosa and has been attributed both adhesive and killing properties against Gram-positive bacteria. However, less is known regarding Gram-negative microorganisms. Therefore, in the present study, the interaction of M. catarrhalis with collagen VI was characterized. We found that collagen VI is upregulated in the airways of COPD patients and exposed upon epithelial desquamation. Ex vivo, we inoculated airway biopsies and fibroblasts from COPD patients with M. catarrhalis. The bacteria specifically adhered to collagen VI-containing matrix fibrils. In vitro, purified collagen VI microfibrils bound to bacterial surface structures. The primary adhesion target was mapped to the collagen VI α₂-chain. Upon exposure to collagen VI, bacteria were killed by membrane destabilization in physiological conditions. These previously unknown properties of collagen VI provide novel insights into the extracellular matrix innate immunity by quickly entrapping and killing pathogen intruders.

Uncontrolled asthmatics have increased FceRI+ and TGF‐β–positive MCTC mast cells and collagen VI in the alveolar parenchyma

“…50 Collagen VI has a unique set of characteristics that includes roles in a plethora of signalling pathways such as for apoptosis, proliferation, inflammation and fibrosis as well as a role in innate immunity with antibacterial activity. 51,52 Collagen VI is not a common fibrillar collagen, but forms a network of thin fibres anchoring collagens types I and III to the reticular basement membrane, and has been found to be increased in idiopathic pulmonary fibrosis and suggested as a biomarker for hepatic fibrosis. 34,53,54 Collagen VI may also counteract apoptosis and alter lung elasticity.…”

Bystander Cells Taking Action

“…The same applies for the Chemistry Prize. Electron microscopy is an essential tool when studying innate immunity [6,7,8,9,10,11]. It will therefore be exciting to see how the new developments will advance the forthcoming research outcome.…”

On PAMPs and DAMPs

“…In a series of elegant experiments the authors show that this effect relies on the PERK-dependent activation of p38 and ERK, and ATF6-mediated basal expression of p38. ER stress is also part of the pathology of chronic obstructive pulmonary disease (COPD) [7] and thus their findings may help to explain why antimicrobial agents such as collagen IV can be upregulated in lung tissue, as observed in biopsies and fibroblasts from COPD patients [8]. …”