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With a Little Help from Their Friends--Viral Innate Immunity Requires Coordination of Three Different Cell Types

(BY RACHEL DERITA, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology) The innate immune system is highly orchestrated and involves many different signals between different cell types to function properly. It is also our first line of defense before the acquired immune system is activated. Therefore, understanding exactly how the innate immune system reacts to viral infections is extremely important for how we treat patients and discover mechanisms of immunity in the future. A recent study from the laboratory of Luis J. Sigal, PhD, Professor of Microbiology and Immunology at Thomas Jefferson University in Philadelphia, reveals a cascade of events between three different cell types in the lymph node. In this study, published in the July 3, 2018 issue of Cell Reports, the activity of the innate immune system after a mousepox infection in the skin of mice was analyzed. The open-access article is titled: “Migratory Dendritic Cells, Group 1 Innate Lymphoid Cells, and Inflammatory Monocytes Collaborate to Recruit NK Cells to the Virus-Infected Lymph Node.” First, it was shown that, after the infection, sentinel cells of the skin called dendritic cells become infected. These cells then rapidly migrate to the lymph node, carrying the virus with them. Once at the draining lymph node, the infected dendritic cells perform two tasks that involve recruiting two other innate immune cell types to the lymph node within the first 24 hours of infection. First, specific molecules called chemokines are released by the infected dendritic cells, which specifically attract inflammatory monocytes. Second, the infected dendritic cells stimulate the small number of natural killer (NK) cells present in the lymph node to produce an inflammatory molecule called interferon gamma. This interferon gamma stimulates the recently arrived monocytes to produce more chemokines and recruit more NK cells to the draining lymph node. The cascade unveiled in this study shows that the crucial players of the innate immune system against viruses, NK cells, require the cooperation of multiple other cell types. Dr. Sigal points out that although it was known that chemokines and cytokines recruited NK cells to infected tissue, the finding that a single cell type (NK cells) needed the participation of multiple cell types in a very specific way is novel. These results could have parallels in other types of viral infection and suggests that deficiencies in multiple cell types of the innate immune system will affect immunity against certain pathogens.

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Artist’s rendering of T-cell and dendritic cell. (Credit: Thinkstock).

[Press release] [Cell Reports article]