Neuroimmunomodulators and Adipocytokines in HIV Infection
Wednesday, June 14, 2006
Presented by the Brain Dysfunction and Neuroimmunology Discussion Group
Organizers: Mady Hornig, Columbia University; Carol Shoshkes Reiss, New York University
The Neuroimmunology Discussion Group focuses on the interface between the immune system and the nervous system both in the brain and in the periphery, in normal and pathological conditions. This highly interdisciplinary group seeks to bring together immunologists and neuroscientists interested in exploring the intersection of these two fields in periodic meetings that will include discussions of basic, clinical, and translational aspects of this emerging field.
5:00 - 7:30: Presentations
Julio Licinio, University of Miami School of Medicine, "The Immune Effects of the Fat Cell Adipokine Leptin: Is it Relevant to HIV Infection?"
Joan Berman, Albert Einstein College of Medicine, "Mechanisms of Transmigration of HIV infected PBMC Across the Blood Brain Barrier: Implications for NeuroAIDS."
Susan Morgello, Mount Sinai School of Medicine, "The Neuroimmunology of HIV Infection."
Joan Berman, "Mechanisms of Transmigration of HIV infected PBMC Across the Blood Brain Barrier: Implications for NeuroAIDS."
Encephalitis and the cognitive impairment associated with AIDS are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether HIV-1 infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, shedding of adhesion molecules, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10, CCL3, or CCL5 did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.
Susan Morgello, "The Neuroimmunology of HIV Infection."
Human Immunodeficiency Virus (HIV) infection causes a complex disorder with profound alterations of peripheral and central nervous system (CNS) immune function over a prolonged period of time. A variety of clinically relevant CNS disorders have been documented in the setting of progressive disease, including HIV-associated dementia (HAD) and minor cognitive motor disorder (MCMD). While therapy directed at HIV has demonstrated efficacy in improving cognitive deficits, there is debate as to whether treatment's primary effects result from immunologic/ virologic control in the periphery or from localized control in the brain. The debate hinges on our understanding of cellular trafficking and the relationship of peripheral immune function to CNS disease. Framed by this debate, the lecture will review the immune alterations seen in peripheral and CNS compartments, their relationship to viral presence, and evidence of the relationship between peripheral markers of immunologic dysfunction and CNS disease.