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Human rhinovirus 16 infection of human macrophages disrupts Arpin expression impairing macrophage internalization: a potential link to exacerbation in chronic obstructive pulmonary disease?

Jamil Jubrail, Kshanti Africano Gomez, Floriane Herit, Anna Mularski, Pierre Bourdoncle, Lisa Oberg, Elisabeth Israelsson, Pierre Regis-Burgel, Gaell Mayer, Danen Cunoosamy, Nisha Kurian, Florence Niedergang
European Respiratory Journal 2020 56: 1063; DOI: 10.1183/13993003.congress-2020.1063
Jamil Jubrail
1Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom
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  • For correspondence: jajubrail@gmail.com
Kshanti Africano Gomez
2Universite de Paris, Institut Cochin, INSERM U1016, CNRS, UMR 8104, Paris, France
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Floriane Herit
2Universite de Paris, Institut Cochin, INSERM U1016, CNRS, UMR 8104, Paris, France
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Anna Mularski
2Universite de Paris, Institut Cochin, INSERM U1016, CNRS, UMR 8104, Paris, France
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Pierre Bourdoncle
2Universite de Paris, Institut Cochin, INSERM U1016, CNRS, UMR 8104, Paris, France
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Lisa Oberg
3Translational Science and Experimental Medicine, Research and Early Development, Respiratory Inflammation and Autoimmunity, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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Elisabeth Israelsson
3Translational Science and Experimental Medicine, Research and Early Development, Respiratory Inflammation and Autoimmunity, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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Pierre Regis-Burgel
4Department of Pneumology, Hospital Cochin, APHP, Paris, France
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Gaell Mayer
5Late Stage Development, Respiratory Inflammation and Autoimmunity, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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Danen Cunoosamy
6Sanofi, Cambridge, Massachusetts, United States of America
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Nisha Kurian
7Precision Medicine, R&D Oncology Unit, AstraZeneca, Massachusetts, United States of America
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Florence Niedergang
2Universite de Paris, Institut Cochin, INSERM U1016, CNRS, UMR 8104, Paris, France
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Abstract

Alveolar macrophages (AM) are crucial to COPD pathogenesis. Evidence suggests they have defective internalisation mechanisms which could drive disease exacerbations where human rhinovirus (HRV) is isolated. We hypothesised HRV infection of macrophages could impair their internalisation functions.

AM or monocyte derived macrophages (MDM) were challenged with HRV16 and then with various triggers and internalisation assessed. Changes to the actin cytoskeleton following HRV16 infection and following particle internalisation were assessed by microscopy.

AM or MDM challenged with HRV16 demonstrated deficient internalisation towards multiple triggers. HRV16 exaggerated deficient internalisation in COPD AM. HRV16 altered the actin cytoskeleton in macrophages driving persistence of actin around internalised particles. Screening for actin regulators affected by HRV16 identified Arpin, a negative Arp2/3 regulator to be significantly decreased after infection. Re-expression of Arpin after infection restored internalisation defects. Further, Arpin depletion impaired internalisation in a similar manner as HRV16 with internalisation stalling at the same point with significantly reduced bacterial uptake. These results confirm that HRV16 targets Arpin in macrophages to impair particle internalisation.

Our results demonstrate HRV16 impairs various macrophage internalisation pathways by targeting Arpin. Hence, HRV16 can hijack macrophage functions and an important phagocytic regulator possibly explaining why COPD patients show secondary bacterial infection post virus infection with increased bacterial numbers.

  • Viruses
  • Exacerbation
  • Monocyte / Macrophage

Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1063.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Human rhinovirus 16 infection of human macrophages disrupts Arpin expression impairing macrophage internalization: a potential link to exacerbation in chronic obstructive pulmonary disease?
Jamil Jubrail, Kshanti Africano Gomez, Floriane Herit, Anna Mularski, Pierre Bourdoncle, Lisa Oberg, Elisabeth Israelsson, Pierre Regis-Burgel, Gaell Mayer, Danen Cunoosamy, Nisha Kurian, Florence Niedergang
European Respiratory Journal Sep 2020, 56 (suppl 64) 1063; DOI: 10.1183/13993003.congress-2020.1063

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Human rhinovirus 16 infection of human macrophages disrupts Arpin expression impairing macrophage internalization: a potential link to exacerbation in chronic obstructive pulmonary disease?
Jamil Jubrail, Kshanti Africano Gomez, Floriane Herit, Anna Mularski, Pierre Bourdoncle, Lisa Oberg, Elisabeth Israelsson, Pierre Regis-Burgel, Gaell Mayer, Danen Cunoosamy, Nisha Kurian, Florence Niedergang
European Respiratory Journal Sep 2020, 56 (suppl 64) 1063; DOI: 10.1183/13993003.congress-2020.1063
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