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A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro
  1. Francesca S M Tang1,2,
  2. Philip M Hansbro3,
  3. Janette K Burgess1,2,4,
  4. Alaina J Ammit5,6,
  5. Katherine J Baines3,
  6. Brian G Oliver1,7
  1. 1Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  2. 2Discipline of Pharmacology, Faculty of Medicine, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia
  3. 3Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia
  4. 4Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
  5. 5Woolcock Emphysema Centre, Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  6. 6Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia
  7. 7Centre for Health Technologies and Molecular Biosciences, School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia
  1. Correspondence to Francesca S M Tang, Woolcock Institute of Medical Research, Level 3, Respiratory Cellular and Molecular Biology Group, 431 Glebe Point Road, Glebe, NSW 2037, Australia; ftan8512{at}


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.

  • Asthma
  • Respiratory Infection
  • Viral infection
  • COPD Exacerbations
  • Innate Immunity
  • Neutrophil Biology

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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  • Contributors FSMT, PMH, AJA, JKB, KJB and BGO provided conception and design of the study. FSMT carried out recruitment, completed all cell biology, laboratory work and data analysis. All authors contributed to the preparation of the manuscript.

  • Funding This study was funded by the National Health and Medical Research Council (NHMRC), Australia. PMH was supported by an NHMRC Principal Research Fellowship, JKB and BGO were supported by NHMRC Career Development Fellowships #1032695 and #1026880.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Human Research Ethics Committee, The University of Sydney.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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