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Discovery of HIV-Friendly Cells in Anogenital Mucosa May Aid Cure Efforts

The discovery of dendritic cells known as CD11c+ offers a pathway to understanding the mechanism behind HIV transmission and how to halt it.

A team of Australian investigators has identified a new type of immune cell in human tissue that acts as an enabler of HIV transmission and infection. Especially prevalent in the vagina and anus, these new cells—called CD11c+ dendritic cells—have the potential to change the landscape of HIV prevention efforts.

Using donated anogenital tissue samples, investigators at the Westmead Institute for Medical Research near Sydney discovered CD11c+ in the epithelial layer of the tissues. This means HIV that comes into contact with these genital tissues will immediately encounter CD11c+ cells, which quickly interact with HIV and efficiently transmit the virus to CD4 cells. In addition to mounting an immune response against HIV, CD4 cells facilitate the replication of HIV cells and lead to their proliferation. In fact, the team concluded that CD11c+ cells are better at driving the HIV infection process than any other dendritic cells studied.

The investigators noted that testing was done using a clinically transmitted/founder strain of HIV as well as a laboratory-adapted strain, both of which supported their findings.

The discovery of CD11c+ has implications for the scientific community’s quest to eradicate HIV, particularly when it comes to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP). Although ART and PrEP are effective when used properly, both regimens have challenges. These include high cost, particularly in lower- and middle-income countries; difficulty with adherence; and potential toxicity.

There also is concern over the effectiveness of PrEP in the presence of inflammation. A recent study conducted in South Africa found that a topical gel containing tenofovir, a PrEP drug, was significantly less effective in women whose vaginas contained high levels of cytokines.

“As cells similar to these called inflammatory dendritic epidermal cells (IEDC) have previously been shown to present in inflamed skin, this could have important implications for transmission across an inflamed mucosa,” Andrew Harman, PhD, associate professor of applied medical sciences in the HIV and Mucosal Immunity Group at the Westmead Institute and the lead author of the Australian study, told Contagion®. “This is important as inflammation has been shown to be strongly associated with sexual transmission in sub-Saharan Africa, and receptive anal intercourse can also be traumatic, leading to tissue damage and inflammation.”

Andrew Harman, PhD

The medical community, of course, is working towards a complete cure for HIV. “In the meantime, the development of simpler and better PrEP/microbicide regimens remains a very high global research priority,” Harman said. “In order to achieve these outcomes, we need a better understanding of how the HIV penetrates and interacts with its target cells in both inflamed and uninflamed anogenital mucosa.”

One of his team’s goals is to pinpoint the mechanism by which HIV binds to CD11c+, which hopefully would enable the creation of novel blocking agents to be used in PrEP regimens. This scenario would mean HIV could be prevented from reaching CD4 cells and spreading.

Another way in which the team’s discoveries could be used is in the development of an HIV vaccine. “To protect against initial infection, the route of transmission and which immune defense mechanisms can be harnessed needs to be understood,” said Harman. “The current targets of broadly neutralizing antibodies (bNAbs), antibody-dependent cytotoxicity, and CD8 T cells may not be enough. Novel innate immune mechanisms in the anogenital mucosa that can be stimulated by vaccine adjuvants could assist.”

Although there’s “not a lot” people can do in the short term to change their levels of HIV-friendly CD11c+ cells, according to Harman, in the future it may be beneficial for people to be aware of their individual CD11c+ levels. “[B]ut this is likely to vary depending on the microbiome,” he added.