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Chemical liberated by leaky gut may allow HIV to infect the brain, Einstein scientists find
Date:8/18/2008

illions of monocytesHIV/GFP-producing monocytes from the HIV/GFP-TG mice, and monocytes from the GFP-TG mice producing GFP aloneand injected each type of monocyte into control mice.

Four days later, the researchers examined the brains of the injected mice to see whether monocytes from the bloodstream had crossed their BBB's. While there was no sign of monocytes in the brains of any of the mice injected with uninfected GFP monocytes, ultrasensitive DNA analysis showed that HIV/GFP monocytes were present at very low levels in the brains of nearly one third of the mice injected with the HIV-producing monocytes. "These results demonstrated very clearly that being infected with HIV somehow gives monocytes the capacity to cross an intact BBB," says Dr. Goldstein. "But we also suspected that something else was making it easier for HIV-infected monocytes to breach the defenses protecting the brain from infection."

In 2006, scientists at the National Institutes of Health had reported that HIV infection breaks down barriers in the intestine that normally prevent intestinal bacteria from entering the bloodstream. The blood of HIV-infected people was found to contain markedly elevated levels of lipopolysaccharide (LPS), a component of certain bacteria that are normally confined to the intestine but leak out due to HIV infection. In addition, previous animal studies had shown that exposure to elevated LPS levels compromised the integrity of the BBB. "So we hypothesized that the combination of HIV-infected monocytes and elevated LPS levels would amplify the ability of HIV to cross the BBB and get into the brain," says Dr. Goldstein.

To test this hypothesis, his team injected control mice with very low doses of LPS that were comparable to the levels in the bloodstream of HIV-infected individuals and would only minimally weaken their BBB's. Three hours later, half the mice were intravenously injected with HIV-and-GFP-producing monocytes, while the rema
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Contact: Michael Heller
mheller@aecom.yu.edu
718-430-4186
Albert Einstein College of Medicine
Source:Eurekalert  

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Chemical liberated by leaky gut may allow HIV to infect the brain, Einstein scientists find
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