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Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: a regulatory mechanism with relevance to asthma.
J Immunol 2012; 188(12):5898-905JI

Abstract

Human rhinoviruses (RV) cause only minor illness in healthy individuals, but can have deleterious consequences in people with asthma. This study sought to examine normal homeostatic mechanisms regulating adaptive immunity to RV in healthy humans, focusing on effects of IFN-αβ and plasmacytoid dendritic cells (pDC) on Th2 immune responses. PBMC were isolated from 27 healthy individuals and cultured with RV16 for up to 5 d. In some experiments, IFN-αβ was neutralized using a decoy receptor that blocks IFN signaling, whereas specific dendritic cell subsets were depleted from cultures with immune-magnetic beads. RV16 induced robust expression of IFN-α, IFN-β, multiple IFN-stimulated genes, and T cell-polarizing factors within the first 24 h. At 5 d, the production of memory T cell-derived IFN-γ, IL-10, and IL-13, but not IL-17A, was significantly elevated. Neutralizing the effects of type-I IFN with the decoy receptor B18R led to a significant increase in IL-13 synthesis, but had no effect on IFN-γ synthesis. Depletion of pDC from RV-stimulated cultures markedly inhibited IFN-α secretion, and led to a significant increase in expression and production of the Th2 cytokines IL-5 (p = 0.02), IL-9 (p < 0.01), and IL-13 (p < 0.01), but had no effect on IFN-γ synthesis. Depletion of CD1c(+) dendritic cells did not alter cytokine synthesis. In healthy humans, pDC and the IFN-αβ they secrete selectively constrain Th2 cytokine synthesis following RV exposure in vitro. This important regulatory mechanism may be lost in asthma; deficient IFN-αβ synthesis and/or pDC dysfunction have the potential to contribute to asthma exacerbations during RV infections.

Authors+Show Affiliations

Lung and Allergy Research Centre, School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. a.pritchard2@uq.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22611238

Citation

Pritchard, Antonia L., et al. "Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: a Regulatory Mechanism With Relevance to Asthma." Journal of Immunology (Baltimore, Md. : 1950), vol. 188, no. 12, 2012, pp. 5898-905.
Pritchard AL, Carroll ML, Burel JG, et al. Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: a regulatory mechanism with relevance to asthma. J Immunol. 2012;188(12):5898-905.
Pritchard, A. L., Carroll, M. L., Burel, J. G., White, O. J., Phipps, S., & Upham, J. W. (2012). Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: a regulatory mechanism with relevance to asthma. Journal of Immunology (Baltimore, Md. : 1950), 188(12), pp. 5898-905. doi:10.4049/jimmunol.1103507.
Pritchard AL, et al. Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: a Regulatory Mechanism With Relevance to Asthma. J Immunol. 2012 Jun 15;188(12):5898-905. PubMed PMID: 22611238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: a regulatory mechanism with relevance to asthma. AU - Pritchard,Antonia L, AU - Carroll,Melanie L, AU - Burel,Julie G, AU - White,Olivia J, AU - Phipps,Simon, AU - Upham,John W, Y1 - 2012/05/18/ PY - 2012/5/22/entrez PY - 2012/5/23/pubmed PY - 2012/8/15/medline SP - 5898 EP - 905 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 188 IS - 12 N2 - Human rhinoviruses (RV) cause only minor illness in healthy individuals, but can have deleterious consequences in people with asthma. This study sought to examine normal homeostatic mechanisms regulating adaptive immunity to RV in healthy humans, focusing on effects of IFN-αβ and plasmacytoid dendritic cells (pDC) on Th2 immune responses. PBMC were isolated from 27 healthy individuals and cultured with RV16 for up to 5 d. In some experiments, IFN-αβ was neutralized using a decoy receptor that blocks IFN signaling, whereas specific dendritic cell subsets were depleted from cultures with immune-magnetic beads. RV16 induced robust expression of IFN-α, IFN-β, multiple IFN-stimulated genes, and T cell-polarizing factors within the first 24 h. At 5 d, the production of memory T cell-derived IFN-γ, IL-10, and IL-13, but not IL-17A, was significantly elevated. Neutralizing the effects of type-I IFN with the decoy receptor B18R led to a significant increase in IL-13 synthesis, but had no effect on IFN-γ synthesis. Depletion of pDC from RV-stimulated cultures markedly inhibited IFN-α secretion, and led to a significant increase in expression and production of the Th2 cytokines IL-5 (p = 0.02), IL-9 (p < 0.01), and IL-13 (p < 0.01), but had no effect on IFN-γ synthesis. Depletion of CD1c(+) dendritic cells did not alter cytokine synthesis. In healthy humans, pDC and the IFN-αβ they secrete selectively constrain Th2 cytokine synthesis following RV exposure in vitro. This important regulatory mechanism may be lost in asthma; deficient IFN-αβ synthesis and/or pDC dysfunction have the potential to contribute to asthma exacerbations during RV infections. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/22611238/Innate_IFNs_and_plasmacytoid_dendritic_cells_constrain_Th2_cytokine_responses_to_rhinovirus:_a_regulatory_mechanism_with_relevance_to_asthma_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&amp;pmid=22611238 DB - PRIME DP - Unbound Medicine ER -