PT  - JOURNAL ARTICLE
AU  - Jamil Jubrail
AU  - Kshanti Africano Gomez
AU  - Floriane Herit
AU  - Anna Mularski
AU  - Pierre Bourdoncle
AU  - Lisa Oberg
AU  - Elisabeth Israelsson
AU  - Pierre Regis-Burgel
AU  - Gaell Mayer
AU  - Danen Cunoosamy
AU  - Nisha Kurian
AU  - Florence Niedergang
TI  - Human rhinovirus 16 infection of human macrophages disrupts Arpin expression impairing macrophage internalization: a potential link to exacerbation in chronic obstructive pulmonary disease?
AID  - 10.1183/13993003.congress-2020.1063
DP  - 2020 Sep 07
TA  - European Respiratory Journal
PG  - 1063
VI  - 56
IP  - suppl 64
4099  - http://erj.ersjournals.com/content/56/suppl_64/1063.short
4100  - http://erj.ersjournals.com/content/56/suppl_64/1063.full
SO  - Eur Respir J2020 Sep 07; 56
AB  - 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.FootnotesCite 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).