Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity
Open Access
- 4 January 2011
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 121 (1), 57-69
- https://doi.org/10.1172/jci44845
Abstract
Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. The protective effect was associated with the preferential expansion of CD4–CD8–, but not CD4+, NKT cells and required T-bet and TLR7. Adoptive transfer of this cell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3+ (Foxp3+) Treg cell population. Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d-restricted fashion. These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.This publication has 58 references indexed in Scilit:
- Tolerance Rather Than Immunity Protects From Helicobacter pylori–Induced Gastric PreneoplasiaGastroenterology, 2011
- Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78The Journal of Experimental Medicine, 2009
- TCR-inducible PLZF transcription factor required for innate phenotype of a subset of γδ T cells with restricted TCR diversityProceedings of the National Academy of Sciences of the United States of America, 2009
- A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivityThe Journal of Experimental Medicine, 2008
- The Transcription Factor PLZF Directs the Effector Program of the NKT Cell LineageImmunity, 2008
- Persistent activation of an innate immune response translates respiratory viral infection into chronic lung diseaseNature Medicine, 2008
- Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17The Journal of Experimental Medicine, 2008
- An African origin for the intimate association between humans and Helicobacter pyloriNature, 2007
- Glycolipid α-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of miceProceedings of the National Academy of Sciences of the United States of America, 2006
- Mechanism of CD1d-restricted natural killer T cell activation during microbial infectionNature Immunology, 2003