Signal inhibitory receptor on leukocytes (SIRL)-1 and leukocyte- associated immunoglobulin-like receptor (LAIR)-1 regulate neutrophil function in infants
Besteman, Sjanna B.; Callaghan, Amie; Hennus, Marije P.; Westerlaken, Geertje H.A.; Meyaard, Linde; Bont, Louis L.
(2020) Clinical Immunology, volume 211, pp. 1 - 9
(Article)
Abstract
During severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we
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aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.
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Keywords: Immune checkpoint, Neutrophil, Neutrophil extracellular traps, Oxidative burst, Respiratory syncytial virus, Immunology and Allergy, Immunology, Journal Article
ISSN: 1521-6616
Publisher: Academic Press Inc.
Note: Funding Information: This work was supported by an internal University Medical Center Utrecht grant of LB. LM is supported by a Vici grant from the Netherlands Organization for Scientific Research (grant no. 91815608 ). Funding Information: This work was supported by an internal University Medical Center Utrecht grant of LB. LM is supported by a Vici grant from the Netherlands Organization for Scientific Research (grant no. 91815608).LB and LM have regular interaction with pharmaceutical and other industrial partners. They have not received personal fees or other personal benefits. LB's institute has received major funding (>?100,000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, the Bill and Melinda Gates Foundation, Nutricia (Danone) and MeMed Diagnostics. LB's institute has received major cash or in kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. University Medical Center Utrecht (UMCU) has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017 (total annual estimate less than ?20,000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, Janssen (total annual estimate less than ?20,000). Dr. Bont is the founding chairman of the ReSViNET Foundation. LM's institute has received funding for investigator-initiated studies from Nextcure, Boehringer Ingelheim, Ono Pharmaceuticals, Ablynx and Janssen. LM received minor funding for consultation from Novo Nordisk, Biogen and Boehringer Ingelheim. None of the other authors have any potential financial conflict of interest related to this manuscript. Funding Information: LB and LM have regular interaction with pharmaceutical and other industrial partners. They have not received personal fees or other personal benefits. LB's institute has received major funding (>€100,000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, the Bill and Melinda Gates Foundation, Nutricia (Danone) and MeMed Diagnostics. LB's institute has received major cash or in kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. University Medical Center Utrecht (UMCU) has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune . UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017 (total annual estimate less than €20,000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, Janssen (total annual estimate less than €20,000). Dr. Bont is the founding chairman of the ReSViNET Foundation. LM's institute has received funding for investigator-initiated studies from Nextcure, Boehringer Ingelheim, Ono Pharmaceuticals, Ablynx and Janssen. LM received minor funding for consultation from Novo Nordisk, Biogen and Boehringer Ingelheim. None of the other authors have any potential financial conflict of interest related to this manuscript. Publisher Copyright: © 2019 Elsevier Inc.
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