Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity.
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ABSTRACT:
SUBMITTER: Chang YJ
PROVIDER: S-EPMC3417123 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
Publications
Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity.
Chang Ya-Jen YJ Kim Hye Young HY Albacker Lee A LA Baumgarth Nicole N McKenzie Andrew N J AN Smith Dirk E DE Dekruyff Rosemarie H RH Umetsu Dale T DT
Nature immunology 20110529 7
Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (T(H)2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown p ...[more]
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Project description:BackgroundAsthma has been considered an immunologic disease mediated by T(H)2 cells and adaptive immunity. However, clinical and experimental observations suggest that additional pathways might regulate asthma, particularly in its nonallergic forms, such as asthma associated with air pollution, stress, obesity, and infection.ObjectivesOur goal was to understand T(H)2 cell-independent conditions that might lead to airway hyperreactivity (AHR), a cardinal feature of asthma.MethodsWe examined a murine model of experimental asthma in which AHR was induced with glycolipid antigens, which activate natural killer T (NKT) cells.ResultsIn this model AHR developed rapidly when mice were treated with NKT cell-activating glycolipid antigens, even in the absence of conventional CD4(+) T cells. The activated NKT cells directly induced alveolar macrophages to produce IL-33, which in turn activated NKT cells, as well as natural helper cells, a newly described non-T, non-B, innate lymphoid cell type, to increase production of IL-13. Surprisingly, this glycolipid-induced AHR pathway required not only IL-13 but also IL-33 and its receptor, ST2, because it was blocked by an anti-ST2 mAb and was greatly reduced in ST2(-/-) mice. When adoptively transferred into IL-13(-/-) mice, both wild-type natural helper cells and NKT cells were sufficient for the development of glycolipid-induced AHR.ConclusionBecause plant pollens, house dust, and some bacteria contain glycolipids that can directly activate NKT cells, these studies suggest that AHR and asthma can fully develop or be greatly enhanced through innate immune mechanisms involving IL-33, natural helper cells, and NKT cells.
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2019-05-11 | GSE131031 | GEO