期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01988
关键词
antimicrobial activity; bronchopulmonary infection; collagen VI; COPD; extracellular matrix; Haemophilus influenzae; innate immunity; pulmonary fibrosis
类别
资金
- Foundation of Anna
- Foundation of Edwin Berger
- Heart Lung Foundation [20150697]
- Swedish Medical Research Council [K2015-57X-03163-43-4]
- Skane County Council's research and development foundation
- Swedish Research Council [7480]
- Swedish Foundation for Strategic Research [SB12-0019]
- Foundation of Crafoord
- Foundation of Johan
- Foundation of Greta Kock
- King Gustav V Memorial Fund
- Lennanders Stiftelse
- Kungliga Fysiografiska Sallskapet i Lund
- Medical Faculty at Lund University
- Swedish Foundation for Strategic Research (SSF) [SB12-0019] Funding Source: Swedish Foundation for Strategic Research (SSF)
Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative human commensal commonly residing in the nasopharynx of preschool children. It occasionally causes upper respiratory tract infection such as acute otitis media, but can also spread to the lower respiratory tract causing bronchitis and pneumonia. There is increasing recognition that NTHi has an important role in chronic lower respiratory tract inflammation, particularly in persistent infection in patients suffering from chronic obstructive pulmonary disease (COPD). Here, we set out to assess the innate protective effects of collagen VI, a ubiquitous extracellular matrix component, against NTHi infection in vivo. In vitro, collagen VI rapidly kills bacteria through pore formation and membrane rupture, followed by exudation of intracellular content. This effect is mediated by specific binding of the von Willebrand A (VWA) domains of collagen VI to the NTHi surface adhesins protein E (PE) and Haemophilus autotransporter protein (Hap). Similar observations were made in vivo specimens from murine airways and COPD patient biopsies. NTHi bacteria adhered to collagen fibrils in the airway mucosa and were rapidly killed by membrane destabilization. The significance in host-pathogen interplay of one of these molecules, PE, was highlighted by the observation that it confers partial protection from bacterial killing. Bacteria lacking PE were more prone to antimicrobial activity than NTHi expressing PE. Altogether the data shed new light on the carefully orchestrated molecular events of the host-pathogen interplay in COPD and emphasize the importance of the extracellular matrix as a novel branch of innate host defense.
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