News: How do immune cells invade tissue?

January 12, 2022 | How do immune cells invade tissue? |

Immunology research update from

In a recent discovery that may aid researchers in identifying new targets for cancer treatment, Belyaeva, et al., 2021 have discovered how immune cells protect themselves when they enter and squeeze between tissue cells.

The timing of when an immune cell invades a tumour cell is difficult to establish. In this present paper, the researchers turned to fruit flies to understand this question. During embryonic development of the fruit fly, macrophages, the dominant immune cell type, travel by means of tissue invasion. The process and time at which this is done has been studied by means of tagging macrophages with a fluorescent protein.

The authors shed light on the process by which cellular changes are needed for tissue invasion and which genes trigger these changes (Figure 1). They reported the assembly of actin filaments to facilitate this process and protect the invading cell. Through a complex cascade involving a variety of proteins, actin filaments are made denser and more connected to each other, forming a stable and protective coating. This leads to the protection of the immune cell’s nucleus from mechanical pressure as it invades the tissue. In addition, they reported, in vivo, that without the actin coating, it becomes difficult for immune cells to infiltrate surrounding tissue.

In their own words:

Our work also suggests a new perspective on the migration of some vertebrate immune cells. We find that altering lamin levels does not normally affect Drosophila macrophage tissue invasion…

A robust cell surface actin layer could allow long-lived cells or those not easily replenished to protect their genome as they move through resistant yet deformable environments. Embryonic Drosophila and vertebrate tissue-resident macrophages migrate into tissues during development, survive into the adult, and serve as founders of proliferative hematopoetic niches. Tissue-resident memory T cells migrate in response to infection in mature animals, are long lived, and are not easily renewed from the blood. Thus, the importance of nuclear mechanics for migration in challenging in vivo environments should be explored for a broader range of immune cells as well as the utilization of cortical actin as a strategy for genomic protection.”

Journal article: Belyaeva, V, et al., 2022. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in DrosophilaPLOS Biology.