Highlights

Monocytes are a type of white blood cell that play an important role in the immune system by fighting invading pathogens. Subhra K. Biswas at the A*STAR Singapore Immunology Network, Fréderic Geissmann of King’s College London and co-workers have now identified a subset of human monocytes that are involved in the surveillance of tissues that have been injured or infected by viruses.

Mice have two subsets of monocytes for different purposes: one subset secretes proinflammatory cytokines in response to pathogens, while the other subset patrols blood vessels to sense tissue damage. However, scientists were unsure if similar monocyte subsets with corresponding functions exist in humans.

The researchers compared the gene expression of the two subsets of mouse monocytes with that of human monocytes. They found that the expression profile of the proinflammatory subset of mouse monocytes was similar to that for human monocytes of subset CD14⁺, which express the cell surface protein CD14. The profile of the mouse monocyte subset involved in patrolling tissues, on the other hand, was similar to that for human monocytes expressing the cell surface protein CD16 along with very low levels of CD14, representing a newly resolved subset of monocytes that the authors call CD14^dimCD16⁺.

When the research team injected human CD14^dimCD16⁺ cells into mice, they found that they attached to and patrolled the blood vessels, while the CD14⁺ cells did not. CD14⁺ cells were quite efficient at engulfing foreign particles, while CD14^dimCD16⁺ cells were not. These functional differences between the human monocyte subsets were similar to the differences in function between the mouse monocyte subsets.

Exposing CD14⁺ cells to bacterial cues led to the production of inflammatory cytokines, while CD14^dimCD16⁺ cells were poor responders. However, treatment of the CD14^dimCD16⁺ cells with herpes or measles virus did lead to cytokine secretion. Biochemical and computational modeling revealed that viral activation induced different signaling pathways in the two human monocyte subsets, which may explain why they have divergent cytokine responses to viral exposure. The researchers also observed CD16⁺ cells in blood vessels in the kidneys of patients with lupus, indicating that this monocyte subset may modulate or induce such autoimmune diseases.

The similarity between mouse and human monocyte subsets suggests that identifying the role of mouse monocytes in mouse models of disease would be likely to parallel the role of human monocytes in the corresponding human disease. “Identification of human monocyte subsets with distinct functions in inflammation and infection may open future options in the development of more specific strategies to target human diseases,” says Biswas.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network.