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Dendritic cells may hold key to elite controllers' immune response
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Dendritic cells, part of the innate human immune system, are better able to recognize HIV-1 infection in elite controllers, which may help this special patient population to control the virus without drug treatment, according to recent findings published in PLoS Pathogens.
“It’s been recognized for a while that these individuals have stronger T-cell immune responses against HIV than other patients,” study researcher Xu G. Yu, MD, investigator at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, said in a press release. “We have shown that dendritic cells, which play a critical role in generating virus-specific T cells, have an improved ability to recognize HIV and build effective immune responses in elite controllers.”
Until recently, the mechanisms supporting enhanced HIV-1–specific T-cell responses in so few patients have been illusive. Dendritic cells, according to Yu and colleagues, “represent the most effective naturally occurring antigen-presenting cells,” capable of inducing human type I interferons (IFN-I) to mount an effective immune response against the virus. In the majority of patients, however, the virus can avoid detection by dendritic cells.
In a series of ex vivo experiments, the researchers found that HIV-1 reverse transcription in dendritic cells of chronic progressors appeared to be blocked at an early stage through the expression of the host protein SAMHD1. This benefited the virus rather than hurt it, they said, because the restriction of HIV-1 replication by SAMHD1 allowed the virus to go undetected. Conversely, the susceptibility of dendritic cells to HIV-1 in elite controllers is what allowed these patients to stage an effective antiviral immune response.
In addition, the exposure of dendritic cells to the virus in elite controllers prompted the upregulation a number of IFN-1–producing genes, including the viral DNA-sensing protein cGAS, which induced HIV-1–specific CD8 T cells to fight infection.
Figure 1. Xu G. Yu, MD, and colleagues have shown that dendritic cells of elite controllers have enhanced abilities to detect HIV-1.
Source: Ragon Institute
The researchers are hopeful that a more complete picture of the mechanisms supporting elite controllers’ ability to fend off the virus in the absence of treatment can serve as a model for developing a functional cure for HIV-1 infection in the general population.
“This study suggests that there is a complex interplay between innate immune recognition and adaptive T cell immune defense that leads to spontaneous HIV immune control,” Yu told Infectious Disease News. – by John Schoen
Disclosure: The researchers report no relevant financial disclosures.
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