Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4 - 06/11/15

Doi : 10.1016/j.jaci.2015.01.042

Ayham Al-Afif, MSc ^a,^{^{∗
These authors contributed equally to this work and are co-first authors.}}, Raidan Alyazidi, MD ^a,^c,^e,^{^{∗
These authors contributed equally to this work and are co-first authors.}}, Sharon A. Oldford, PhD ^a, Yan Y. Huang, PhD ^a,^c, Christine A. King, PhD ^a,^{^{§
Dr King is currently affiliated with Upstate Medical University, State University of New York, Syracuse, New York.}}, Nico Marr, PhD ^d, Ian D. Haidl, PhD ^a, Robert Anderson, PhD ^a,^c,^d,^⁎,^{^{‡
These authors contributed equally to this work.}} , Jean S. Marshall, PhD ^a,^b,^⁎,^{^{‡
These authors contributed equally to this work.}}
^a Department of Microbiology and Immunology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada
^b Department of Pathology, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada
^c Department of Pediatrics, Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada
^d Canadian Center for Vaccinology, Izaak Walter Killam Health Centre, Halifax, Nova Scotia, Canada
^e Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

^∗Corresponding author: Jean S. Marshall, PhD, or Robert Anderson, PhD, Department of Microbiology and Immunology, Dalhousie University, 5850 College St, Halifax, Nova Scotia B3H 4R2, Canada.

Abstract

Background

Respiratory syncytial virus (RSV) causes severe respiratory tract infections, which might have a role in the development of airway hyperreactivity. Mast cells are important effector cells in allergy, with sentinel cell roles in host defense. However, the role of mast cells in response to RSV infection is unknown.

Objective

Human mast cell responses to RSV were investigated with a view to better understanding the role of mast cells in RSV-induced disease.

Methods

Human cord blood–derived mast cells and the HMC-1 mast cell line were exposed to RSV or UV-inactivated RSV. Viral gene and protein expression were evaluated by using PCR and flow cytometry. The expression of interferon-stimulated genes and selected mediators were evaluated by using quantitative PCR and ELISA.

Results

Human mast cells expressed multiple RSV genes after exposure to RSV, and a small percentage of mast cells supported RSV antigen protein expression. RSV induced mast cells to upregulate production of chemokines, including CCL4, CCL5, and CXCL10, as well as type I interferons, and interferon-stimulated gene expression. However, production of the granulocyte chemoattractants CXCL8 and CCL11 was not induced. Antibody blockade of the type I interferon receptor on human cord blood–derived mast cells reduced the RSV-mediated induction of CXCL10 and CCL4 but not CCL5. Leukotriene C₄ production by mast cells was not enhanced by exposure to RSV.

Conclusion

Despite low levels of infection, human mast cells produce multiple chemokines in response to RSV through mechanisms that include responses to type I interferons. Such mast cell responses might enhance effector cell recruitment during RSV-induced disease.

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Key words : Mast cells, viral infection, innate immunity, respiratory infection, chemokines, interferons, respiratory syncytial virus

Abbreviations used : CBMC, DC, ISG56, LTC₄, MOI, MX1, NK, pDC, qPCR, RSV

Plan

Methods

Cell lines

Primary mast cells

RSV propagation and treatment

Inoculation conditions

Plaque assays

Fluorescence-activated cell sorting staining and analysis

Human mast cells support RSV antigen expression

CBMCs produce selective chemokines in response to RSV

CBMCs do not produce LTC₄ in response to RSV

RSV-induced mast cell production of selected chemokines depends on early type I interferons

Discussion

Supported by the Canadian Institutes of Health Research (CIHR) grant no. MOP10966. The CIHR had no role in the study design; the collection, analysis, and interpretation of data; or the writing and submission process for this manuscript.

Disclosure of potential conflict of interest: This study was funded by the Canadian Institutes of Health Research (CIHR) grant no. MOP10966. S. A. Oldford has received support for travel to meetings for this study or other purposes from the CIHR, as has I. D. Haidl, and A. Al-Afif. J. S. Marshall is employed by Dalhousie University, which has received or has grants pending from the CIHR and AllerGen NCE. The rest of the authors declare that they have no relevant conflicts of interest.

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Vol 136 - N° 5

P. 1346 - novembre 2015 Retour au numéro

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Respiratory syncytial virus infection of primary human mast cells induces the selective production of type I interferons, CXCL10, and CCL4 - 06/11/15

Abstract

Background

Objective

Methods

Results

Conclusion

Plan

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