Pilot Award Recipient: Marina Jerebtsova, PhD

Dr. Jerebtsova Picture

Impaired Pulmonary Macrophage Migration in HIV-Tg Mouse Model of Lung Injury

January 11, 2017
In HIV-infected patients on antiretroviral therapy pulmonary complications have been shifted from opportunistic infections to non-communicable disease. The mechanism of increased prevalence of noninfectious disease in HIV patients with controlled viremia is unclear. During early stages of HIV infection, the intestinal epithelial barrier suffers extensive damage, leading to translocation of the gut microbes and microbial products into circulation where they can induce systemic inflammation and pathobiology of distal organs. Reactivation of HIV provirus in specific immune cell subsets together with systemic inflammation can lead to severe defects in pulmonary immune responses. The respiratory tract is constantly exposed to various environmental pathogens and stress therefore fast activation of innate immune response and fast resolution of this activation is important for the lung-specific immune response.
 
The researchers have established a model of lung innate immune system activation using LPS administration in HIV transgenic mice, and preliminary studies demonstrate that LPS induces mortality and leads to the abnormal lung leukocytes infiltration in HIVTg mice. Amount of lung-infiltrated neutrophil is increased. A migration pattern of lung-infiltrated macrophages is changed from alveolar and interstitial sites to capillary and lung periphery. Higher levels of HIV genes expression in lung macrophages compared to peritoneal macrophages are found. We hypothesize that lung-specific high oxygen environment activates HIV-1 provirus in macrophages and impairs their migration, reducing resolution of neutrophil activation. In Aim 1 this project will characterize lung inflammation and leukocytes infiltration after LPS injection. In Aim 2 the project will study trans-endothelial migration of HIV-infected macrophages at different oxygen levels. The proposed study will identify a novel mechanism of HIV-associated non-infectious lung disease.