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Neonatal BCG vaccination influences cytokine responses to toll-like receptor ligands and heterologous antigens


Freyne, B and Donath, S and Germano, S and Gardiner, K and Casalaz, D and Robins-Browne, RM and Amenyogbe, N and Messina, NL and Netea, MG and Flanagan, KL and Kollmann, T and Curtis, N, Neonatal BCG vaccination influences cytokine responses to toll-like receptor ligands and heterologous antigens, Journal of Infectious Diseases, 217, (11) pp. 1798-1808. ISSN 0022-1899 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 The Authors.

DOI: doi:10.1093/infdis/jiy069


Background: BCG vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The underlying mechanisms remain uncertain, but long-term modulation of the innate immune response (trained immunity) may be involved.

Methods: Whole-blood specimens, collected 7 days after randomization from 212 neonates enrolled in a randomized trial of neonatal BCG vaccination, were stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses.

Results: -vaccinated infants had increased production of interleukin 6 (IL-6) in unstimulated samples and decreased production of interleukin 1 receptor antagonist, IL-6, and IL-10 and the chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and monocyte chemoattractant protein 1 (MCP-1) following stimulation with peptidoglycan (TLR2) and R848 (TLR7/8). BCG-vaccinated infants also had decreased MCP-1 responses following stimulation with heterologous pathogens. Sex and maternal BCG vaccination status interacted with neonatal BCG vaccination.

Conclusions: Neonatal BCG vaccination influences cytokine responses to TLR ligands and heterologous pathogens. This effect is characterized by decreased antiinflammatory cytokine and chemokine responses in the context of higher levels of IL-6 in unstimulated samples. This supports the hypothesis that BCG vaccination modulates the innate immune system. Further research is warranted to determine whether there is an association between these findings and the beneficial nonspecific (heterologous) effects of BCG vaccine on all-cause mortality.

Item Details

Item Type:Refereed Article
Keywords:Bacille Calmette-Guérin, immunisation, heterologous, nonspecific, trained immunity
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Flanagan, KL (Dr Katie Flanagan)
ID Code:130604
Year Published:2018
Web of Science® Times Cited:56
Deposited By:Medicine
Deposited On:2019-02-06
Last Modified:2022-08-25

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