Recurrent respiratory syncytial virus infection in a CD14 deficient patient
Besteman, Sjanna B; Phung, Emily; Raeven, Henriette H M; Amatngalim, Gimano D; Rumpret, Matevž; Crabtree, Juliet; Schepp, Rutger M; Rodenburg, Lisa W; Siemonsma, Susanna G; Verleur, Nile; van Slooten, Rianne; Duran, Karen; van Haaften, Gijs; Beekman, Jeffrey M; Chang, Lauren A; Meyaard, Linde; van der Bruggen, Tjomme; Berbers, Guy A M; Derksen, Nicole; Nierkens, Stefan; Morabito, Kaitlyn M; Ruckwardt, Tracy J; Kurt-Jones, Evelyn A; Golenbock, Douglas; Graham, Barney S; Bont, Louis J
(2022) The Journal of infectious diseases, volume 226, issue 2, pp. 258 - 269
(Article)
Abstract
BACKGROUND: Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism is unknown. We aimed to determine the role of CD14-mediated immunity in the pathogenesis of recurrent RSV infection. METHODS: We performed genotyping and longitudinal immunophenotyping of the first patient with a genetic CD14 deficiency who
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developed recurrent RSV infection. We analyzed gene expression profiles and interleukin (IL)-6 production by patient peripheral blood mononuclear cells in response to RSV pre- and post-fusion (F) protein. We generated CD14-deficient human nasal epithelial cells cultured at air-liquid interface (HNEC-ALI) of patient-derived cells and after CRISPR-based gene editing of control cells. We analyzed viral replication upon RSV infection. RESULTS: Sanger sequencing revealed a homozygous single-nucleotide deletion in CD14, resulting in absence of the CD14 protein in the index patient. In vitro, viral replication was similar in wild-type and CD14-/- HNEC-ALI. Loss of immune cell CD14 led to impaired cytokine and chemokine responses to RSV pre- and post-F protein, characterized by absence of IL-6 production. CONCLUSIONS: We report an association of recurrent RSV bronchiolitis with a loss of CD14 function in immune cells. Lack of CD14 function led to defective immune responses to RSV pre- and post-F protein without a change in viral replication.
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Keywords: CD14, Cytokines, Humans, Leukocytes, Mononuclear/metabolism, Lipopolysaccharide Receptors/deficiency, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Toll-like receptor, epithelium, monocyte, respiratory syncytial virus, Infectious Diseases, Immunology and Allergy, Case Reports, Journal Article
ISSN: 0022-1899
Publisher: Oxford University Press
Note: Funding Information: This work was funded by an internal University Medical Centre Utrecht Grant (to L. J. B.). D. G. and E. A. K.-J. report grants from National Institute of Health. The rest of the authors declare that they have no relevant conflicts of interest. Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
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