Cytokine and chemokine profiles in a human respiratory disease model of Ebola virus

Abstract

Abstract Category A agents, such as Ebola virus, pose a great risk to national security because of high rates of transmission and mortality and the gravity of impact to public health. The use of Ebola virus as a bioweapon is a significant concern, and rapid diagnostics, safe vaccines, and efficacious therapeutics are needed. The Mucosal Tissue Equivalent (MTE) component of the MIMIC™ lung mucosal model is an in vitro/ex vivo respiratory tissue model comprised of human lung epithelial cells that mimics the vascularized lower airway alveolar tissue micro-environment. The use of the MTE allows for the inclusion of human immune components, which may be a better predictor of the human immune response than animal models. In this study, Ebola virus was applied at the air-liquid interface of the differentiated human epithelium and expression of cytokines was measured. Peripheral blood mononuclear cells (PBMCs) were applied to apical layer of the MTEs prior to inoculation with Ebola virus (Kikwit). We quantified cytokines and chemokines using supernatants serially collected on days 0, 3, 6, 9, and 15 post infection. In the infected MTEs containing human PBMCs, we detected pro-inflammatory cytokines, colony stimulating factors and endothelial growth factors. This “cytokine storm” would be expected to play a role in inflammation, recruitment of cells to the site of infection, and induction of a specific immune response to acute viral infection in humans. This human lung infection model will be used to evaluate existing therapeutic antibody and vaccine candidates for Ebola virus. Going forward, this system may provide a more rapid, relevant and cost effective means to evaluate vaccine candidates than can be accomplished by using animal models.