Probiotic Bacillus spp. enhance TLR3-mediated TNF signalling in macrophages
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Probiotic Bacillus spp. enhance TLR3-mediated TNF signalling in macrophages. / Winther, Katrine Damgaard; Boll, Erik Juncker; Sandvang, Dorthe; Williams, Andrew R.
In: Immunology, Vol. 171, No. 3, 2024, p. 402-412.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Probiotic Bacillus spp. enhance TLR3-mediated TNF signalling in macrophages
AU - Winther, Katrine Damgaard
AU - Boll, Erik Juncker
AU - Sandvang, Dorthe
AU - Williams, Andrew R.
N1 - Publisher Copyright: © 2023 John Wiley & Sons Ltd.
PY - 2024
Y1 - 2024
N2 - Probiotics have been reported to have immunomodulatory properties in the context of infectious disease and inflammation, although the underlying mechanisms are not fully understood. Here, we aimed to determine how different probiotic bacterial strains modulated macrophage function during TLR3 stimulation mimicking viral infection. We screened 14 different strains for their ability to modulate TNF-α, IL-6 IL-10, IFN-α, IFN-β and IFN-γ secretion in RAW 264.7 macrophages with or without poly(I:C) stimulation. Seven strains were selected for further analysis using primary porcine alveolar macrophages. In-depth transcriptomic analysis on alveolar macrophages was conducted for two strains. Most strains induced a synergistic effect when co-incubated with poly(I:C) resulting in increased levels of IL-6 and TNF-α secretion from RAW 264.7 cells. This synergistic effect was found to be TLR2 independent. Only strains of Bacillus spp. could induce this effect in alveolar macrophages. Transcriptomic analysis indicated that the increased TNF-α secretion in alveolar macrophages after co-incubation with poly(I:C) correlated with significant upregulation of TNF and IL23A-related pathways. Collectively, our data show that probiotic bacteria possess strain-dependent immunomodulatory properties that may be harnessed to enhance innate immune responses to pathogens.
AB - Probiotics have been reported to have immunomodulatory properties in the context of infectious disease and inflammation, although the underlying mechanisms are not fully understood. Here, we aimed to determine how different probiotic bacterial strains modulated macrophage function during TLR3 stimulation mimicking viral infection. We screened 14 different strains for their ability to modulate TNF-α, IL-6 IL-10, IFN-α, IFN-β and IFN-γ secretion in RAW 264.7 macrophages with or without poly(I:C) stimulation. Seven strains were selected for further analysis using primary porcine alveolar macrophages. In-depth transcriptomic analysis on alveolar macrophages was conducted for two strains. Most strains induced a synergistic effect when co-incubated with poly(I:C) resulting in increased levels of IL-6 and TNF-α secretion from RAW 264.7 cells. This synergistic effect was found to be TLR2 independent. Only strains of Bacillus spp. could induce this effect in alveolar macrophages. Transcriptomic analysis indicated that the increased TNF-α secretion in alveolar macrophages after co-incubation with poly(I:C) correlated with significant upregulation of TNF and IL23A-related pathways. Collectively, our data show that probiotic bacteria possess strain-dependent immunomodulatory properties that may be harnessed to enhance innate immune responses to pathogens.
KW - bacteria
KW - cytokines
KW - macrophage
KW - probiotics
KW - TLRs
U2 - 10.1111/imm.13721
DO - 10.1111/imm.13721
M3 - Journal article
C2 - 38030377
AN - SCOPUS:85178249591
VL - 171
SP - 402
EP - 412
JO - Immunology
JF - Immunology
SN - 0019-2805
IS - 3
ER -
ID: 385688746