Key Immune System Cell Reduces Secretion of Defense Protein in HIV-Associated Dementia Patients

Researchers at the San Francisco Veterans Affairs Medical Center and UCSF have discovered that an important protein normally secreted by macrophages, the scavenger cells of the immune system, is secreted at significantly reduced levels in patients with HIV-related dementia.

The protein, known as lysozyme, is an anti-viral, anti-bacterial enzyme found in human monocytes (which differentiate into macrophages), which circulate in the blood stream but migrate as macrophages to the brain and other organs to fight infection.

Monocyte/macrophages are known to become infected by HIV in the bloodstream, but unlike the immune system’s T-cells, they are not killed when infected. (The virus continues to infect the macrophages even in the presence of highly active antiretroviral therapy (HAART).) Instead, the cells serve as a reservoir for the virus. As the cells sometimes migrate to the brain, they can give the virus access to the organ early in the infection.

The discovery that HIV-infected macrophages secrete lysozyme at dramatically reduced levels in HIV-demented patients suggests that the macrophages are no longer highly activated, but are, instead, dysfunctional and thus unable to fight HIV-1 or other infections, says lead researcher Lynn Pulliam, PhD, associate chief of staff for research at the SF Veterans Affairs Medical Center and UCSF professor of laboratory medicine and medicine.

In earlier studies, the researchers have shown that certain immune-system molecules secreted by HIV-infected monocyte/macrophages are toxic to the brain’s neurons, or nerve cells. The new study identifies for the first time, says Pulliam, a specific protein in HIV-infected macrophages that is not secreted in patients with HIV-dementia.

It’s possible, she says, that the protein could prove to be a marker to monitor the progression of HIV-associated dementia and serve as a possible target for treatment.

In their study, the researchers investigated whether there were distinctions in macrophage protein secretions in 11 people with HIV-related dementia, 13 HIV patients who did not have dementia and nine individuals who did not have HIV. Working with blood samples, they used the tools of proteomics to create profiles of the proteins secreted by the cells.

The study showed that, while the enzyme was secreted at greatly reduced levels in the macrophages of HIV-associated dementia patients, it was “abundantly secreted” by the cells in the other two groups of patients, the researchers reported.

Pulliam advocated continuing research into macrophages as a barometer of immune system health.

The study was published in the April 23 issue of the journal AIDS.

Co-authors of the study were Bing Sun, MD, PhD, UCSF postdoctoral fellow in Laboratory Medicine, and Hans Rempel, PhD, research scientist, Northern California Institute for Research and Education.

The study was supported by the National Institutes of Health.