AUTHOR: Melissa Fishman

A new study led by the Dang Lab at the Ragon Institute, published in Science Immunology, details how immune cells can travel from the bloodstream into the lungs. Specifically, they have succeeded in identifying a macrophage-driven, metabolite-based mechanism of immunosuppressive cell positioning in inflamed lung tissue.

The Dang Lab achieved this discovery by studying the fungus Cryptococcus neoformans, which can cause infections and severe cases of pneumonia. In the case of such exposure, the body will send chemical signals that will alarm the immune system to prevent inflammation and preserve lung tissue by travelling from the bloodstream to the infected tissue. However, it has long been a mystery as to how these immune cells react once they arrive in the lung tissue. This gap in the literature presented a unique avenue for scientific exploration which has now been solved by the Dang lab.

According to the study, macrophages—immune cells that help organize and carry out the body’s defense against infections—produce molecules called oxysterols that attract T helper 2 (TH2) cells. Surprisingly, instead of helping fight the infection, TH2 cells reduce the macrophages’ ability to kill the invading fungus.

The researchers found that when they removed a key molecule called GPR183, TH2 cells could no longer move toward the site of infection. As a result, macrophages became more effective at destroying the fungus. These findings suggest that preventing TH2 cells from reaching fungal infections could be a promising new strategy for improving the body’s ability to eliminate fungal diseases.

This finding has identified a new way to interpret how the body tells immune cells to move throughout our systems. It is now clear that these cells may have a GPS-like system that directs their path rather than simply determining how many cells might be present.

This study was co-authored by Yufan Zheng, Hannah E.Dobson, Makheni Jean Pierre, Lillian B.LeBlanc, Chinaemerem U. Onyishi, Dominic P.Golec, Nathan Carrillo, Anshu Deewan, Claudia A.Rivera, Eduard Ansaldo, Pamela L.Schwartzberg, and Eric V. Dang. Collaborators included researchers from NIH, Georgetown University, the University of Pennsylvania, and The National Institute of Allergy and Infectious Diseases.