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Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.

Publication ,  Journal Article
Fitzpatrick, AM; Mohammad, AF; Huang, M; Stephenson, ST; Patrignani, J; Kamaleswaran, R; Grunwell, JR
Published in: The Journal of allergy and clinical immunology
December 2023

Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population.We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n = 16; no sensitization, n = 36).Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid [poly(I:C)] as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase, and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation.A total of 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (ie, more myeloperoxidase and extracellular DNA) and less neutrophil proinflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (ie, M2) phenotype in sensitized children and a more proinflammatory (ie, M1) phenotype in nonsensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled health care were also higher in children without aeroallergen sensitization after enrollment.Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at type 2-high inflammation.

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Published In

The Journal of allergy and clinical immunology

DOI

EISSN

1097-6825

ISSN

0091-6749

Publication Date

December 2023

Volume

152

Issue

6

Start / End Page

1433 / 1443

Related Subject Headings

  • Respiratory Sounds
  • Peroxidase
  • Neutrophils
  • Inflammation
  • Immunophenotyping
  • Humans
  • DNA
  • Cytokines
  • Child, Preschool
  • Allergy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fitzpatrick, A. M., Mohammad, A. F., Huang, M., Stephenson, S. T., Patrignani, J., Kamaleswaran, R., & Grunwell, J. R. (2023). Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing. The Journal of Allergy and Clinical Immunology, 152(6), 1433–1443. https://doi.org/10.1016/j.jaci.2023.08.010
Fitzpatrick, Anne M., Ahmad F. Mohammad, Min Huang, Susan T. Stephenson, James Patrignani, Rishikesan Kamaleswaran, and Jocelyn R. Grunwell. “Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.The Journal of Allergy and Clinical Immunology 152, no. 6 (December 2023): 1433–43. https://doi.org/10.1016/j.jaci.2023.08.010.
Fitzpatrick AM, Mohammad AF, Huang M, Stephenson ST, Patrignani J, Kamaleswaran R, et al. Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing. The Journal of allergy and clinical immunology. 2023 Dec;152(6):1433–43.
Fitzpatrick, Anne M., et al. “Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.The Journal of Allergy and Clinical Immunology, vol. 152, no. 6, Dec. 2023, pp. 1433–43. Epmc, doi:10.1016/j.jaci.2023.08.010.
Fitzpatrick AM, Mohammad AF, Huang M, Stephenson ST, Patrignani J, Kamaleswaran R, Grunwell JR. Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing. The Journal of allergy and clinical immunology. 2023 Dec;152(6):1433–1443.
Journal cover image

Published In

The Journal of allergy and clinical immunology

DOI

EISSN

1097-6825

ISSN

0091-6749

Publication Date

December 2023

Volume

152

Issue

6

Start / End Page

1433 / 1443

Related Subject Headings

  • Respiratory Sounds
  • Peroxidase
  • Neutrophils
  • Inflammation
  • Immunophenotyping
  • Humans
  • DNA
  • Cytokines
  • Child, Preschool
  • Allergy