A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro.
BACKGROUND
Rhinovirus (RV) infections are the major precipitant of asthma exacerbations. While neutrophilic lung inflammation occurs during such infections, its role remains unclear. Neutrophilic inflammation is associated with increased asthma severity and steroid refractory disease. Neutrophils are vital for controlling infections but also have immunomodulatory functions. Previously, we found that neutrophils respond to viral mimetics but not replication competent RV. We aimed to investigate if neutrophils are activated and/or modulate immune responses of monocytes during RV16 infection.


METHODS
Primary human monocytes and autologous neutrophils were cocultured with or without RV16, in direct contact or separated by transwells. RV16-stimulated monocytes were also exposed to lysed neutrophils, neutrophil membrane components or soluble neutrophil intracellular components. Interleukin 6 (IL-6) and C-X-C motif (CXC)L8 mRNA and proteins were measured by quantitative PCR and ELISA at 24 hours.


RESULTS
RV16 induced IL-6 and CXCL8 in monocytes, but not neutrophils. RV16-induced IL-6 and CXCL8 from monocytes was reduced in the presence of live neutrophils. Transwell separation abolished the inhibitory effects. Lysed neutrophils inhibited RV16-induced IL-6 and CXCL8 from monocytes. Neutrophil intracellular components alone effectively inhibited RV16-induced monocyte-derived IL-6 and CXCL8. Neutrophil intracellular components reduced RV16-induced IL-6 and CXCL8 mRNA in monocytes.


CONCLUSIONS
Cell contact between monocytes and neutrophils is required, and preformed neutrophil mediator(s) are likely to be involved in the suppression of cytokine mRNA and protein production. This study demonstrates a novel regulatory function of neutrophils on RV-activated monocytes in vitro, challenging the paradigm that neutrophils are predominantly proinflammatory.
Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia Discipline of Pharmacology, Faculty of Medicine, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Francesca S M
FS
Tang
Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.
Philip M
PM
Hansbro
Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia Discipline of Pharmacology, Faculty of Medicine, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
Janette K
JK
Burgess
Woolcock Emphysema Centre, Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.
Alaina J
AJ
Ammit
Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.
Katherine J
KJ
Baines
Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia Centre for Health Technologies and Molecular Biosciences, School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.
Brian G
BG
Oliver
D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010850:Picornaviridae Infections / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012229:Rhinovirus / Q000276:immunology*
D015850:Interleukin-6; D016209:Interleukin-8
Asthma; COPD Exacerbations; Innate Immunity; Neutrophil Biology; Respiratory Infection; Viral infection