The Role Of Cd44 And Its Isoforms In S. Aureus-induced Inflammation

Abstract

Hospital-acquired S. aureus infections have long been an issue in public health in the United States, but community-acquired infections are now on the rise as well. While the S. aureus bacteria present can be treated withare sensitive too numerous antibiotics, there is no known effective treatment for the superantigen activity within produced by the bacteria. Superantigens are virulence factors associated withsecreted by S. aureus that cause complications during infection due to cross-linking of MCH class II antigens on antigen presenting cells and T-cell receptors. T This process to stimulates a large numbers of T cells causing increased pro-inflammatory cytokine production, vascular leak, and severe inflammation [5]. This study examines the role of CD44 during S. aureus-induced inflammation and identifies CD44 isoforms CD44v6v7 and CD44v8v10 as potential targets for treatment of the effects associated with superantigen- infectioninduced inflammation. The results show that CD44 isoforms CD44v6v7 and CD44v8-v10 are elevated in PBMC’s isolated from patients bacteremic with S. aureus and in mice exposed to S. aureus. This could make them Consequently, these isoforms may be potential targets to reduce the effects of superantigen activity. The role of CD44 is shown through the use of CD44KO mice, which have reduced pro-inflammatory cytokine production and reduced immune cell migration into the lungs after S. aureus exposure when compared to WT C57BL/6 mice. The CD44KO mice do, however, show increased bacterial loads in the lungs. This suggests that while not all CD44 molecules can be targeted due to reduced clearance of bacteria, perhaps the isoforms CD44v6v7 and CD44v8-v10 can. Future studies to target CD44v6v7 and/or CD44v8-v10 to examine the effects of the immune response following S. aureus infection are warranted.