Oral Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

ADAMTS5 - A critical enzyme in T cell mediated immune responses (#109)

Meagan McMahon 1 , Lenny Izzard 1 , Suneel Apte 2 , Ralph Tripp 3 , Daniel McCulloch 1 , John Stambas 1
  1. School of Medicine, Deakin University, Geelong, VIC, Australia
  2. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, United States
  3. Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States

Extracellular matrix (ECM) enzymes, such as the ADAMTS (A disintegrin-like and metalloproteinase with thrombospondin-1 motifs) family, play a significant role in remodelling the ECM to facilitate immune cell migration, cell adhesion, and cleavage of ECM proteins. It has been suggested that these properties may allow ADAMTS enzymes to modulate immune cell trafficking. ADAMTS5, a member of the ADAMTS family, can specifically cleave ECM proteoglycans and has a prolific role in osteoarthritis pathogenesis. In this study, we infected Adamts5-/- mice with X31 influenza virus (104 pfu/mouse) and measured their response to virus infection at 3, 7 and 10 days post infection. Adamts5-/- mice showed greater weight loss and produced higher lung viral loads when compared to WT counterparts following infection. Moreover we observed a reduced proportion of lung macrophages in Adamts5-/- mice at day 3 post infection. Critically, we also uncovered decreased numbers of NP366 and PA224 influenza specific CD8+ T cells in the spleens and lungs of Adamts5-/- mice that were associated with a corresponding increase in these populations in the mediastinal lymph node (MLN) at day 7 post infection. We therefore hypothesise that the ADAMTS5 enzyme through its ECM remodelling capabilities, is a critical component involved in facilitating T cell migration from the draining MLN to the lung and periphery, following influenza virus infection.