Abstract
Influenza virus infection is an important cause of severe asthma exacerbations, but it remains unclear how a Th1‐mediated antiviral response triggers a prototypical Th2 disease. We investigated CD4+ T cells and group 2 innate lymphoid cells (ILC2s) in influenza virus‐infected mice. We found that ILC2s accumulated in the lung rapidly after influenza virus infection, but the induction of IL‐5 and IL‐13 secretion was delayed and concomitant with T cell activation. In an influenza‐induced exacerbation of allergic airway inflammation model we noticed an initial reduction of ILC2 numbers and cytokine production in broncho‐alveolar lavage compared to chronic house dust mite (HDM)‐mediated airway inflammation alone. ILC2s phenotype was characterized by low T1/ST2, ICOS, KLRG1, and CD25 expression, resembling naïve ILC2s. The contribution of ILC2s to type 2 cytokine production in the early stage of the influenza‐induced exacerbation was limited. In contrast, T cells showed increased IL‐4 and IL‐5 production when exposed to both HDM and influenza virus. Upon virus clearance, ILC2s regained an activated T1/ST2highICOShighKLRG1highCD25high phenotype paired with cytokine production and were major contributors to the type 2 cytokine milieu. Collectively, our data indicate that both T cells and ILC2s contribute to influenza‐induced exacerbation of allergic airway inflammation, but with different kinetics.
Highlights
Asthma exacerbations are often provoked by respiratory viruses, rhinovirus and RSV [1, 2]
Influenza virus infection induces major changes in expressed genes in the lungs We aimed to identify the activation patterns of T cells and ILC2s in mice infected with the X31 H3N2 strain of influenza virus
We used intracellular flow cytometry to evaluate the capacity of Th2 cells and ILC2 to produce cytokines. These analyses revealed that the numbers of IL-4+ and IL-5+ CD4+ T cells were significantly enhanced at day 4 and 7 of the X31-induced exacerbation of house dust mite (HDM)-mediated allergic airway inflammation, when compared to influenza virus infection or HDM-challenge alone (Fig. 5A)
Summary
Asthma exacerbations are often provoked by respiratory viruses, rhinovirus and RSV [1, 2]. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. In conjunction with the pre-existing inflammatory environment in asthma patients, loss of barrier function provides a partial explanation for the clinical observations that indicate an association between influenza virus infection and asthma exacerbation.
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