The lung is an important interface between the body and the outside environment: with each breath, a surface of roughly 100 square meters exchanges oxygen for carbon dioxide. More than 10,000 liters of air pass adult lungs every day and with this come numerous viruses, bacteria and pollutants, which need to be prevented from entering the body.
To defend the organism from these intruders, the lungs harbor their own arsenal of highly specialized immune cells that are equipped to maintain the balance between host defense and tissue quiescence. However, how this balanced immune homeostasis in lungs emerged after birth, was largely unexplored. Now, for the first time, the group of Sylvia Knapp showed with the help of mouse models that the very first breath of a newborn releases crucial signals that shape the lifelong immunological milieu of lungs.
The study, published in Cell Reports (DOI:10.1016/j.celrep.2017.01.071), reveals that the mechanical forces of spontaneous ventilation at birth lead to the release of interleukin (IL)-33, a cytokine with a wide-range of effects: So-called “type 2 innate lymphoid cells” (ILC2s) follow the IL-33 signal and migrate into the lung tissue, where they release IL-13, another cytokine. This second signal determines the faith of alveolar macrophages by inducing the anti-inflammatory M2 phenotype.
The described mechanisms are crucial in achieving lung quiescence after the first contact with the outside world. However, these processes at the same time increase the susceptibility to bacterial infections, such as bacterial pneumonia - the primary cause of death by an infectious disease in Western countries.
Simona Saluzzo, Anna-Dorothea Gorki, Batika M. J. Rana, Rui Martins, Seth Scanlon, Philipp Starkl, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Omar Sharif, Joanna M. Warszawska, Helen Jolin, Ildiko Mesteri, Andrew N. J. McKenzie und Sylvia Knapp. First-breath induced type-2 pathways shape the lung immune environment. Cell Reports, February 21, 2017. DOI:10.1016/j.celrep.2017.01.071
This study was supported by the Austrian Science Funds (FWF, DK CCHD), the Vienna Science and Technology Fund (WWTF) and grants from the Medical Research Council and the Wellcome Trust.