Respiratory syncytial virus infection activates IL-13–producing group 2 innate lymphoid cells through thymic stromal lymphopoietin

Matthew T. Stier, Melissa H. Bloodworth, Shinji Toki, Dawn C. Newcomb, Kasia Goleniewska, Kelli L. Boyd, Marc Quitalig, Anne L. Hotard, Martin L. Moore, Tina V. Hartert, Baohua Zhou, Andrew N. McKenzie, R. Stokes Peebles

Research output: Contribution to journalArticle

74 Scopus citations


Background Respiratory syncytial virus (RSV) is a major health care burden with a particularly high worldwide morbidity and mortality rate among infants. Data suggest that severe RSV-associated illness is in part caused by immunopathology associated with a robust type 2 response. Objective We sought to determine the capacity of RSV infection to stimulate group 2 innate lymphoid cells (ILC2s) and the associated mechanism in a murine model. Methods Wild-type (WT) BALB/c, thymic stromal lymphopoietin receptor (TSLPR) knockout (KO), or WT mice receiving an anti-TSLP neutralizing antibody were infected with the RSV strain 01/2-20. During the first 4 to 6 days of infection, lungs were collected for evaluation of viral load, protein concentration, airway mucus, airway reactivity, or ILC2 numbers. Results were confirmed with 2 additional RSV clinical isolates, 12/11-19 and 12/12-6, with known human pathogenic potential. Results RSV induced a 3-fold increase in the number of IL-13–producing ILC2s at day 4 after infection, with a concurrent increase in total lung IL-13 levels. Both thymic stromal lymphopoietin (TSLP) and IL-33 levels were increased 12 hours after infection. TSLPR KO mice did not mount an IL-13–producing ILC2 response to RSV infection. Additionally, neutralization of TSLP significantly attenuated the RSV-induced IL-13–producing ILC2 response. TSLPR KO mice displayed reduced lung IL-13 protein levels, decreased airway mucus and reactivity, attenuated weight loss, and similar viral loads as WT mice. Both 12/11-19 and 12/12-6 similarly induced IL-13–producing ILC2s through a TSLP-dependent mechanism. Conclusion These data demonstrate that multiple pathogenic strains of RSV induce IL-13–producing ILC2 proliferation and activation through a TSLP-dependent mechanism in a murine model and suggest the potential therapeutic targeting of TSLP during severe RSV infection.

Original languageEnglish (US)
Pages (from-to)814-824.e11
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Sep 1 2016



  • Group 2 innate lymphoid cells
  • IL-13
  • IL-33
  • respiratory syncytial virus
  • thymic stromal lymphopoietin
  • type 2 immunity (T2)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Stier, M. T., Bloodworth, M. H., Toki, S., Newcomb, D. C., Goleniewska, K., Boyd, K. L., Quitalig, M., Hotard, A. L., Moore, M. L., Hartert, T. V., Zhou, B., McKenzie, A. N., & Peebles, R. S. (2016). Respiratory syncytial virus infection activates IL-13–producing group 2 innate lymphoid cells through thymic stromal lymphopoietin. Journal of Allergy and Clinical Immunology, 138(3), 814-824.e11.