NFKB ACTIVATION IN PNEUMOCOCCUS AND SIV-COINFECTED LUNGS

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Simian Immunodeficiency Virus (SIV) infection of macaques is an important animal model for the acquired immunodeficiency syndrome (AIDS) that recapitulates most features of HIV infection, including CNS disease. Alcohol has been shown to exacerbate other disease states, notably pneumonia. Activation of NFKB is known to be an initial step in the development of disease. To determine if SIV infection of macaques exacerbates the activation of NFKB and its subsequent translocation from the cytoplasm to the perinuclear area we obtained bronchoalveolar lavage (BAL) fluids from rhesus macaques before and after infection with pneumococcus. We also examined lung tissues obtained from the same macaques at necropsy. In situ hybridization and immunohistochemistry was performed on these tissues to determine if there is colocaliztion of the virus and NFKB within nucleus of cells. In addition to increased expression in type II pneumocytes, NFKB was activated in SIV-infected macrophages and also in adjacent macrophages that have recently migrated into lungs in response to pneumococcus challenge. These experiments can be only performed in the rhesus macaque model due to obtaining samples before infection with SIV and at timed intervals thereafter. Immunohistochemistry and in situ hybridization indicate that inoculation of an SIV-infected macaque with pneumococcus leads to an increase in NFKB activation and increased numbers of SIV-infected cells within the lungs when compared with cells derived from the same lung in the same animal previously.