Neonatal BCG Vaccination Reduces Interferon-gamma Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial
SourceThe Journal of Infectious Diseases, 221, 12, (2020), pp. 1999-2009
Article / Letter to editor
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The Journal of Infectious Diseases
SubjectRadboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences
BACKGROUND: BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization. METHODS: A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands. RESULTS: Compared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-gamma) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-gamma in response to heterologous stimulation and TLR ligands. Reduced IFN-gamma responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-gamma response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination. CONCLUSIONS: BCG vaccination leads to changes in IFN-gamma responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen.
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