Rhinoviruses are among the most common viruses to infect man, causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity; however, their function during rhinovirus infection in vivo is undefined. In RV-infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expressions of IL-15 and IL-15Rα, which in turn were required for NK- and CD8(+) T-cell responses. Treatment with IL-15-IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9, and CXCL10 followed by recruitment of activated, IFN-γ-expressing NK, CD8(+), and CD4(+) T cells. Treating infected IFNAR1(-/-) mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ, and CXCL9 (but not CXCL10) expression also followed by NK-, CD8(+)-, and CD4(+)-T-cell recruitment and activation. We have demonstrated that type I IFN-induced IFN-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. Importantly, we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment, which in turn was sufficient to drive IFN-γ expression and lymphocyte responses.

IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection / A., Jayaraman; D. J., Jackson; S. D., Message; R. M., Pearson; J., Aniscenko; Caramori, Gaetano; P., Mallia; A., Papi; B., Shamji; M., Edwards; J., Westwick; T., Hansel; L. A., Stanciu; S. L., Johnston; N. W., Bartlett. - In: MUCOSAL IMMUNOLOGY. - ISSN 1933-0219. - 7:5(2014), pp. 1151-1164. [10.1038/mi.2014.2]

IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection

CARAMORI, Gaetano;
2014-01-01

Abstract

Rhinoviruses are among the most common viruses to infect man, causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity; however, their function during rhinovirus infection in vivo is undefined. In RV-infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expressions of IL-15 and IL-15Rα, which in turn were required for NK- and CD8(+) T-cell responses. Treatment with IL-15-IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9, and CXCL10 followed by recruitment of activated, IFN-γ-expressing NK, CD8(+), and CD4(+) T cells. Treating infected IFNAR1(-/-) mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ, and CXCL9 (but not CXCL10) expression also followed by NK-, CD8(+)-, and CD4(+)-T-cell recruitment and activation. We have demonstrated that type I IFN-induced IFN-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. Importantly, we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment, which in turn was sufficient to drive IFN-γ expression and lymphocyte responses.
2014
IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection / A., Jayaraman; D. J., Jackson; S. D., Message; R. M., Pearson; J., Aniscenko; Caramori, Gaetano; P., Mallia; A., Papi; B., Shamji; M., Edwards; J., Westwick; T., Hansel; L. A., Stanciu; S. L., Johnston; N. W., Bartlett. - In: MUCOSAL IMMUNOLOGY. - ISSN 1933-0219. - 7:5(2014), pp. 1151-1164. [10.1038/mi.2014.2]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2964115
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