Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3480400

Documents

In Collections

This item can be found in the following collections:

Santos, C.C. dos; Walburg, K.V.; Veen, S. van; Wilson, L.G.; Trufen, C.E.M.; Nascimento, I.P.; ... ; Haks, M.C. (2022)

Recombinant BCG-LTAK63 vaccine candidate for tuberculosis induces an inflammatory profile in human macrophages

Article / Letter to editor
Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-beta, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts...Show moreTuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-beta, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB.Show less
tuberculosis
BCG vaccination
recombinant BCG
gene expression profiling
cytokine profiling
primary human macrophages
immune response
All authors
Santos, C.C. dos; Walburg, K.V.; Veen, S. van; Wilson, L.G.; Trufen, C.E.M.; Nascimento, I.P.; Ottenhoff, T.H.M.; Leite, L.C.C.; Haks, M.C.
Date
2022-06-01
Journal
Vaccines
Volume
10
Issue
6
DOI
doi:10.3390/vaccines10060831
Link
https://www.mdpi.com/2076-393X/10/6/831