Increased autoimmune disease activity in MRL-lpr mice following influenza infection. (135.21)

Abstract

Abstract Influenza virus infection induces IFNα and TNFγ, which have been linked to increased severity of select autoimmune diseases. Influenza also stimulates TRL3 and TLR7, which are associated with increased kidney damage in mouse models of lupus. Therefore it seems likely that influenza infection of individuals with systemic lupus erythematosus, or lupus, would accelerate autoimmune disease progression. We used the MRL-lpr mouse model of spontaneous lupus-like disease to examine the impact of influenza infection on end stage organ damage. Influenza infection of MRL-lpr mice resulted in significant peri-vascular cellular infiltrates in the kidneys, composed primarily of CD4+ T cells. The infected mice also had accelerated proteinuria and lymphadenopathy of the cervical and mediastinal lymph nodes. Infection also resulted in a transient but significant increase in the concentration of anti-cardiolipin antibodies, but no changes in other autoimmune specificities. Experiments are underway to determine if this end-stage organ damage is dependent upon virus replication or if exposure to viral proteins, such as following vaccination, would result in increased kidney damage. This model will provide a unique system to dissect the immune-pathogen interaction in an autoimmune disease setting. These data will also provide valuable information on how infection impacts autoimmune disease development and progression.