OPN receptor expression on immune effector cells in RSV infection is regulated by NKT cells

Abstract

Abstract RSV infection in early life predisposes to asthma later in life. Role of aberrant immune responses to childhood viral infections is well documented. Involvement of myeloid (mDC) and plasmacytoid (pDC) Dendritic Cells (DC) and Natural Killer T-cells (NKT) has been reported. Osteopontin (OPN) modulates the immune responses to viral infections. The current studies looked into the role of NKT cells in regulating the OPN receptor expression in RSV infection on DC, T and B cells, which will elucidate the role of OPN in preventing RSV-induced hyper-reactive airway and asthma. Five-day-old BALB/C and NKT−/−(CD1d−/−) mice were infected intranasally with RSV; and expression of OPN receptors (CD44 and CD51/61) were examined at designated post-infection days on lung mDC (CD11blo/−CD11chiCD45Rlo/−), pDC (CD11blo/−CD11clo/−CD45Rhi), T (CD3+) and B (CD19+) cells by flow cytometry. Expression of CD44 and CD51/61 were decreased on mDC, pDC, T and B cells in RSV infected wild pups compared to the control pups. On the other hand, OPN receptor expression was enhanced in the RSV-infected NKT−/− pups compared to the infected wild pups and uninfected NKT−/− pups suggesting a regulatory role of NKT cells on expression of OPN receptors, as RSV-infected NKT−/− pups had significantly increased CD44 and CD51/CD61 expression on DC and lymphocytes. Thus, decreased OPN receptor expression during RSV infection very likely diminishes the action of endogenous OPN allowing skewed polarization of DC and subsequent T cell responses. Therefore, abolishing the action of NKT cells to augment the action of endogenous OPN; and/or administration of exogenous OPN warrant further investigation as a new therapeutic strategy against RSV-associated asthma.