Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants

Huaqiong Huang, Jordy Saravia, Dahui You, Aaron J. Shaw, Stephania Cormier

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. Interleukin (IL)-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared with adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, whereas exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A+γδ T cells compared with PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalImmunology and Cell Biology
Volume93
Issue number2
DOIs
StatePublished - Feb 12 2015

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Inflammasomes
Respiratory Syncytial Virus Infections
Somatostatin-Secreting Cells
Interleukin-17
Respiratory Syncytial Viruses
T-Lymphocytes
Blood Cells
Newborn Infant
Mucus
Fetal Blood
Cytokines
Virus Diseases
Tretinoin
Interleukin-1
Lung Diseases
Interleukin-6
Pneumonia
Inflammation
Lung
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants. / Huang, Huaqiong; Saravia, Jordy; You, Dahui; Shaw, Aaron J.; Cormier, Stephania.

In: Immunology and Cell Biology, Vol. 93, No. 2, 12.02.2015, p. 126-135.

Research output: Contribution to journalArticle

Huang, Huaqiong ; Saravia, Jordy ; You, Dahui ; Shaw, Aaron J. ; Cormier, Stephania. / Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants. In: Immunology and Cell Biology. 2015 ; Vol. 93, No. 2. pp. 126-135.
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