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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Parasitic Diseases Laboratory » Research » Publications at this Location » Publication #354410

Research Project: Molecular Approaches to Control Intestinal Parasites that Affect the Microbiome in Swine and Small Ruminants

Location: Animal Parasitic Diseases Laboratory

Title: S1P dependent inter organ trafficking of group 2 innate lymphoid cells supports host defense

item HUANG, YUEFENG - National Institutes Of Health (NIH)
item MAO, KAIRUI - National Institutes Of Health (NIH)
item CHEN, XI - National Institutes Of Health (NIH)
item SUN, MING-AN - National Institutes Of Health (NIH)
item KAWABE, TAKESHI - National Institutes Of Health (NIH)
item LI, WEIZHE - National Institutes Of Health (NIH)
item USHER, NICHOLAS - Cornell University
item ZHU, JINFANG - National Institutes Of Health (NIH)
item Urban, Joseph
item PAUL, WILLIAM - National Institutes Of Health (NIH)
item GERMAIN, RONALD - National Institutes Of Health (NIH)

Submitted to: Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2017
Publication Date: 1/5/2018
Citation: Huang, Y., Mao, K., Chen, X., Sun, M., Kawabe, T., Li, W., Usher, N., Zhu, J., Urban Jr, J.F., Paul, W.E., Germain, R.N. 2018. S1P dependent inter organ trafficking of group 2 innate lymphoid cells supports host defense. Science. 359:114–119.

Interpretive Summary: It has been long known that the immune system responds to specific molecules produced by invading pathogens to develop acquired immunity that specifically and vigorously responds to a second exposure to the pathogen. The acquired response is very specific but takes some time to develop and often requires multiple exposures to generate protective immune responses. More recently, it is apparent that there are innate or rapid response elements to the immune system that begin to activate immunity the very first time that a pathogen enters the host. The response is more dependent on common pathogen molecules compared to very specific ones in order for the host to see and respond quickly to a common threat. Many of these responses are generated at mucosal sites such as the lungs and intestine where invading pathogens first enter the host. The current work demonstrates that the innate cells are local to the site of the invasion but there are also signals that are sent throughout the body to activate more cell production in the bone marrow and migration of those innate immune cells to the site of the invasion as a way to expand and enhance the level of the response. This scenario primes the system to activate the acquired immune response that subsequently matures. The study describes the use of a parasitic nematode infection in mice to provide a stimulation of the innate immune system in the lungs and intestine in order to study the features of this response. This information is important to those interested in both animal and human health and the regulators of immunity and inflammation that generates an appropriate response to infection.

Technical Abstract: Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a tissue-resident manner or can move between sites during infection is unclear. We show here that IL-25- or helminthic infection-induced inflammatory ILC2s are not tissue-resident but circulating cells, which arise from resting ILC2s residing in intestinal lamina propria and then migrate to mesenteric lymph nodes, spleen, lung, and liver. IL-25 induces rapid proliferation of the intestinal ILC2s and a change in their sensitivity to S1P-mediated chemotaxis, leading to lymphatic entry, blood circulation, and accumulation in periphery sites, including the lung where they contribute to anti-helminth defense and tissue repair. Our finding of cytokine-driven expansion and migration of innate lymphocytes, a behavioral parallel to the antigen-driven priming, expansion, and migration of adaptive lymphocytes to effector sites in distant tissues, provides a significant advance in our overall understanding of ILCs and indicates that ILCs complement adaptive immunity by providing both local and distant site effector protection during infection.