[HTML][HTML] BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner
VACM Koeken, LCJ de Bree… - The Journal of …, 2020 - Am Soc Clin Investig
VACM Koeken, LCJ de Bree, VP Mourits, SJ Moorlag, J Walk, B Cirovic, RJW Arts, M Jaeger…
The Journal of clinical investigation, 2020•Am Soc Clin InvestigBACKGROUND Induction of innate immune memory, also termed trained immunity, by the
antituberculosis vaccine bacillus Calmette-Guérin (BCG) contributes to protection against
heterologous infections. However, the overall impact of BCG vaccination on the
inflammatory status of an individual is not known; while induction of trained immunity may
suggest increased inflammation, BCG vaccination has been epidemiologically associated
with a reduced incidence of inflammatory and allergic diseases. METHODS We investigated …
antituberculosis vaccine bacillus Calmette-Guérin (BCG) contributes to protection against
heterologous infections. However, the overall impact of BCG vaccination on the
inflammatory status of an individual is not known; while induction of trained immunity may
suggest increased inflammation, BCG vaccination has been epidemiologically associated
with a reduced incidence of inflammatory and allergic diseases. METHODS We investigated …
BACKGROUND
Induction of innate immune memory, also termed trained immunity, by the antituberculosis vaccine bacillus Calmette-Guérin (BCG) contributes to protection against heterologous infections. However, the overall impact of BCG vaccination on the inflammatory status of an individual is not known; while induction of trained immunity may suggest increased inflammation, BCG vaccination has been epidemiologically associated with a reduced incidence of inflammatory and allergic diseases.
METHODS
We investigated the impact of BCG (BCG-Bulgaria, InterVax) vaccination on systemic inflammation in a cohort of 303 healthy volunteers, as well as the effect of the inflammatory status on the response to vaccination. A targeted proteome platform was used to measure circulating inflammatory proteins before and after BCG vaccination, while ex vivo Mycobacterium tuberculosis– and Staphylococcus aureus–induced cytokine responses in peripheral blood mononuclear cells were used to assess trained immunity.
RESULTS
While BCG vaccination enhanced cytokine responses to restimulation, it reduced systemic inflammation. This effect was validated in 3 smaller cohorts, and was much stronger in men than in women. In addition, baseline circulating inflammatory markers were associated with ex vivo cytokine responses (trained immunity) after BCG vaccination.
CONCLUSION
The capacity of BCG to enhance microbial responsiveness while dampening systemic inflammation should be further explored for potential therapeutic applications.
FUNDING
Netherlands Organization for Scientific Research, European Research Council, and the Danish National Research Foundation.
The Journal of Clinical Investigation