Lung ILC2s make IL-13 in response to early-life rhinovirus infection
Published Online: June 7, 2014
Early-life wheezing-associated rhinovirus infections have been linked to asthma development in high-risk infants and children. Could infection with human rhinovirus—the common cold virus—play a causative role in the development of asthma? Or is wheezing simply a marker of pre-existing asthma? Birth cohort studies, while uncovering strong associations between early-life viral infection and airway function, do not provide causal information. Such data can only be provided by an animal model. Unlike other respiratory viruses, rhinovirus causes minimal cytotoxicity and infects relatively few cells, suggesting that an animal model of early life rhinovirus infection may be useful.
In a study recently published in The Journal of Allergy and Clinical Immunology, Hong and colleagues exposed six day-old and eight week-old BALB/c mice to human rhinovirus. This mouse strain is relatively susceptible to allergic airways disease. Rhinovirus infection in neonatal mice increased lung IL-13 and IL-25 production, whereas production of IFN-γ, IL-12p40 and TNF-α was suppressed. RV infection of mature mice produced the opposite results, with robust induction of type 1 cytokines but minimal induction of IL-13 or IL-25.
Hong and colleagues also found that the population of IL-13-secreting type 2 innate lymphoid cells (ILC2s) was expanded after rhinovirus infection in neonatal but not mature mice. ILC2s were the major cell type secreting IL-13. Finally, anti–IL-25 neutralizing antibodies attenuated ILC2 expansion, mucous hypersecretion and airways responsiveness. These findings suggest that, under the right circumstances, early-life rhinovirus infection could contribute to asthma development by provoking age-dependent, IL-25-driven type 2 immune responses.
This new research establishes that ILC2s make IL-13 in response to viral infection in neonatal animals. Further, the authors found a developmental difference in the ILC2
response between neonates and adults which was based on the production of IL-25. Finally, rhinovirus-induced IL-13 secretion and ILC2 expansion were long-lived, at least 21 days after infection. It is therefore conceivable that ILC2s could produce type 2 cytokines for extended periods, perhaps in response to subsequent infection or allergen exposure. Further characterization of this immune pathway might lead to new molecular and cellular targets for the prevention of asthma.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.