A Trait of The Rare Few Whose Bodies Naturally Control HIV: “Trained” Immune Cells; Scientists Discover That “Elite Controllers” Have Myeloid Dendritic Cells That Display Characteristics of Trained Innate Immune Cells

Immunity often calls to mind the adaptive immune response, made up of antibodies and T cells that learn to fight specific pathogens after infection or vaccination. But the immune system also has an innate immune response, which uses a set number of techniques to provide a swift, non-specialized response against pathogens or support the adaptive immune response. In the past few years, however, scientists have found that certain parts of the innate immune response can, in some instances, also be trained in response to infectious pathogens, such as HIV. Xu Yu, MD, a Core Member of the Ragon Institute of Massachusettes General Hospital, MIT and Harvard, and colleagues recently published a study in the Journal of Clinical Investigation which showed that elite controllers, a rare subset of people whose immune system can control HIV without the use of drugs, have myeloid dendritic cells, part of the innate immune response, that display traits of a trained innate immune cell. The open-access article was published online on May 3, 2021 and is titled “Long Noncoding RNA MIR4435-2HG Enhances Metabolic Function of Myeloid Dendritic Cells from HIV-1 Elite Controllers” (https://www.jci.org/articles/view/146136). "Using RNA-sequencing technology, we were able to identify one long-noncoding RNA called MIR4435-2HG that was present at a higher level in elite controllers' myeloid dendritic cells, which have enhanced immune and metabolic states," says Dr. Yu. "Our research shows that MIR4435-2HG might be an important driver of this enhanced state, indicating a trained response." Myeloid dendritic cells' primary job is to support T cells, which are key to the elite controllers' ability to control HIV infection. Because MIR4435-2HG was found in higher levels only in cells from elite controllers, Dr. Yu explains, it may be part of a learned immune response to infection with HIV. Myeloid dendritic cells with increased MIR4435-2HG also had higher amounts of a protein called RPTOR, which drives metabolism. This increased metabolism may allow the myeloid dendritic cells to better support the T cells controlling the HIV infection.