ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity

Meagan McMahon, Siying Ye, Leonard Izzard, Daniel Dlugolenski, Ralph A. Tripp, Andrew G.D. Bean, Daniel R. McCulloch, John Stambas

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)
15 Downloads (Pure)

Abstract

The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs) protein family, cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis. However, its contribution to viral pathogenesis and immunity is currently undefined. Here, we use a combination of in vitro and in vivo models to show that ADAMTS5 enzymatic activity plays a key role in the development of influenza-specific immunity. Influenza virus infection of Adamts5-/-mice resulted in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican, an ADAMTS5 proteoglycan substrate. Our research emphasises the importance of ADAMTS5 expression in the control of influenza virus infection and highlights the potential for development of ADAMTS5-based therapeutic strategies to reduce morbidity and mortality.

Original languageEnglish
Article numbere1002580
Pages (from-to)1-22
Number of pages22
JournalPLoS Biology
Volume14
Issue number11
DOIs
Publication statusPublished - 17 Nov 2016
Externally publishedYes

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