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Biomedical subjects

E C Breij

Publications and source records attributed to E C Breij.

3 recordsLinked to original sources

Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesis.

Although it has been almost 20 years since the first cases of acquired immunodeficiency syndrome (AIDS) were documented, the pathogenesis is still not completely understood. Interactions between major histocompatibility complex (MHC) Class I and human immunodeficiency virus (HIV), resulting in down-regulation of MHC-I surface expression, have been reported to contribute to pathogenesis by suppressing the host's immune response. Interactions between MHC Class II and HIV have also been described, but it is unclear how these contribute to the pathogenesis. MHC-II surface expression on HIV-infected monocytes and monocytic cell lines has been described to be increased as well as decreased when compared to uninfected control monocytes. HIV-specific mechanisms appear to down-regulate MHC-II expression on blood monocytes during HIV-1 infection, whereas host mechanisms up-regulate MHC-II expression in response to infection of blood monocytes as well as brain macrophages. A balance between these two may determine MHC-II expression levels in individual patients. Altogether, HIV seems to be able to benefit from both low and high levels of MHC-II surface expression. The first results in reduced immune surveillance of the host, allowing the virus to replicate faster; the second increases infectivity of the virus as a result of higher MHC-II density on macrophages and virion particles.

Acquired Immunodeficiency Syndrome↗

Spatial structure, contrast polarity and motion integration.

It has been shown that in the initial stages of motion processing, the ON and OFF pathways stay more or less separated. There is evidence that this distinction between motion signals from opposite contrast polarities remains at least partly intact in the integration stage of local motion information. At the same time, interactions between the two systems are also apparent. Here we constructed stimuli that contained a constant number of moving checks. The checks were either assigned only one contrast polarity, or contrast polarity was distributed across the checks either randomly or evenly. We investigated how the spatial configuration of the moving stimulus affected direction discrimination thresholds for the different polarity distributions. Our results provide new evidence for contrast-sign-specific integration of local motion signals within areas of limited size, and inhibitory interactions between these separate ON and OFF motion sensor pools.

Contrast Sensitivity↗

Interactions between HIV-infected monocyte-derived macrophages and human brain microvascular endothelial cells result in increased expression of CC chemokines.

The presence of perivascular monocytic infiltration is a major hallmark of HIV-1-associated dementia. Since CC chemokines are chemoattractant cytokines that are able to attract T cells and monocytes/macrophages to sites of inflammation, and since infiltrating monocytes/macrophages remain in close contact with the brain endothelium, we investigated whether interactions between HIV-1-infected macrophages and brain endothelium result in an altered chemokine production. We found an increased mRNA expression of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and RANTES by macrophages after HIV-1 infection. Interactions between HIV-infected macrophages and brain microvascular endothelial cells resulted in an additional upregulation of chemokine mRNA expression, during cell-cell contact as well as in a trans-well system. Since IL-1 beta can function as a modulator of chemokine expression we investigated if interleukin-1 beta could be involved in the regulation of chemokine induction. Coculturing of HIV-infected macrophages and endothelial cells resulted in immune-activation as indicated by increased mRNA expression of IL-1 beta. Subsequently, addition of a neutralizing antibody against IL-1 beta resulted in altered chemokine expression by macrophages, but not by endothelial cells. Thus, IL-1 beta appears to play a major role in the regulation of chemokines during cellular interactions in HIV-associated dementia, but other factors may also be involved.

Antibodies↗