Dendritic Cells for Antiviral Immune Responses

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August 25, 2023

Team from the University Hospital Erlangen and FAU Identifies Differentiation Step Essential for Antiviral Immune Responses

Dendritic cells are crucial for orchestrating immune responses: They patrol all tissues of the body, capturing invaders like viruses and bacteria, and subsequently trigger an immune response tailored to the pathogen. A research team led by the University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg (FAU) has now demonstrated that dendritic cells must undergo a specific maturation step to induce particularly effective immune responses. The results have been published in the renowned journal “Proceedings of the National Academy of Sciences (PNAS).”

Dendritic cells, named for their numerous surface branches, populate various parts of the human body. When they encounter and engulf a pathogen or tumor cell, they migrate to the lymph nodes and initiate immune responses tailored to the invader or tumor. As such, dendritic cells are central regulators of the immune system. To trigger the appropriate immune response, dendritic cells possess a multitude of receptors that recognize pathogens and interact with other immune cells. In recent years, it has become clear that dendritic cells are composed of various subgroups, some of which differ significantly in their functions. One of these subsets of dendritic cells, known as conventional dendritic cells type I (cDC1), is particularly important for combating tumors and viral infections.

Now, a team led by Dr. Lukas Heger and Prof. Dr. Diana Dudziak from the University Hospital Erlangen has demonstrated that the cDC1 cell population constitutes a heterogeneous mixture of various maturation stages. Among these cDC1 cells, some undergo an additional maturation step and carry a specific receptor (XCR1) on their surface, granting them special properties: Only these cDC1 cells produce messengers that activate other immune cells like natural killer cells. These messengers are also crucial for protecting body cells from viral infection. By identifying this surface molecule, future therapies could selectively target cells that induce robust immune responses.

The data also show that immature dendritic cells can be differentiated into fully functional cDC1 cells with the help of specific growth factors. As cDC1 cells in all examined tissues in the study appeared to be a mixture of precursor and effector cells, this differentiation process seems to be a continuous process in the body, one that could be negatively influenced by pathogens and tumor cells. They could prevent differentiation, thus inhibiting a strong immune response. Such negative influence could open up new therapeutic approaches to enhance immune responses.