In the Zone: Natural Killer Cells as Protectors of Marginal Zone Macrophages

Abstract

By Sanjeeth Rajaram, Medical Sciences

Advisor: Stephen Waggoner

Abstract: Natural killer (NK) cells are white blood cells that are essential for immunity against various pathogens. However, in individuals that have weakened immune systems, such as those with chronic infections, NK cells also play a significant role in maintaining the spleen's marginal zone. The marginal zone acts as a first line of defense against blood-circulating pathogens (e.g. Listeria monocytogenes) by continuously filtering the blood and capturing microbes present within. This function is mainly performed by marginal zone macrophages, a specialized cell therein, and helps prevent the spread of microbes throughout the host. Importantly, we discovered that chronically infected mice lacking NK cells had lost the vast majority of their marginal zone macrophages. Loss of these vital immune cells increases susceptibility of chronically infected mice to lethal listeria infection, likely due to severe spread of the microbe to vital host organs including the lung and the brain. This bacterial spread is reminiscent of lethal Listeriosis cases in patients with weakened immune systems. By uncovering the protective roles NK cells play in preserving vital immune cells, we can identify ways to protect individuals with weakened immune systems from lethal bacterial infections.