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dc.contributor.authorHughes, Bethany
dc.contributor.authorBurton, Charlotte
dc.contributor.authorReese, Abigail
dc.contributor.authorJabeen, Maisha
dc.contributor.authorWright, Carl
dc.contributor.authorKhoshaein, Nika
dc.contributor.authorMarsh, Elizabeth
dc.contributor.authorPeachell, Peter
dc.contributor.authorSun, Shao-Cong
dc.contributor.authorDockrell, David
dc.contributor.authorMarriott, Helen
dc.contributor.authorSabroe, Ian
dc.contributor.authorCondliffe, Alison
dc.contributor.authorPrince, Lynne
dc.contributor.authorWillis, Jessica
dc.identifier.citationHughes, B. et al. (2019) 'Pellino-1 regulates immune responses to Haemophilus influenzae in models of inflammatory lung disease', Frontiers in Immunology, 10:1721. doi: 10.3389/fimmu.2019.01721.en_US
dc.description.abstractNontypeable Haemophilus influenzae (NTHi) is a frequent cause of lower respiratory tract infection in people with chronic obstructive pulmonary disease (COPD). Pellino proteins are a family of E3 ubiquitin ligases that are critical regulators of TLR signalling and inflammation. The aim of this study was to identify a role for Pellino-1 in airway defence against NTHi in the context of COPD. Pellino-1 is rapidly upregulated by LPS and NTHi in monocyte-derived macrophages (MDMs) isolated from individuals with COPD and healthy control subjects, in a TLR4 dependent manner. C57BL/6 Peli1-/- and wild-type (WT) mice were subjected to acute (single LPS challenge) or chronic (repeated LPS and elastase challenge) airway inflammation followed by NTHi infection. Both WT and Peli1-/- mice develop airway inflammation in acute and chronic airway inflammation models. Peli1-/- animals recruit significantly more neutrophils to the airway following NTHi infection which is associated with an increase in the neutrophil chemokine, KC, in bronchoalveolar lavage fluid as well as enhanced clearance of NTHi from the lung. These data suggest that therapeutic inhibition of Pellino-1 may augment immune responses in the airway and enhance bacterial clearance in individuals with COPD.en_US
dc.description.sponsorshipThis work was supported by British Lung Foundation awards (RG14-4 and PPRG16-11 both to LRP) and Medical Research Council award (MR/L009374/1 to IS and MRNO2995X/1 to DD). The University of Sheffield funds (where annual budgets allow) APCs for open access charges.en_US
dc.publisherFrontiers Mediaen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.subjectInflammation, Lung, Immunity, Pellino-1, Haemophilus influenzaeen_US
dc.titlePellino-1 regulates immune responses to Haemophilus influenzae in models of inflammatory lung disease.en_US
dc.contributor.departmentUniversity of Sheffielden_US
dc.contributor.departmentUniversity of Derbyen_US
dc.contributor.departmentUniversity of Oxforden_US
dc.contributor.departmentUniversity of Edinburghen_US
dc.contributor.departmentUniversity of Texas MD Anderson Cancer Centeren_US
dc.identifier.journalFrontiers in Immunologyen_US

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Attribution-NonCommercial-NoDerivs 3.0 United States
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