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. 2017 Oct 23;9(10):1156. doi: 10.3390/nu9101156

Table 4.

Probiotic modulation of signaling pathways in macrophage cells.

Probiotic Effector Response Cells/Cell Line Reference
L. casei Shirota L. fermentum MS15 L. plantarumNCIMB41605 L. salivarius NCIMB41606 B. breve NCIMB 8807 TNFα: Increased—CD14hi M1/M2 Decreased—CD14lo M1/M2
IL-6: Decreased—M2
NF-κB: Decreased—M1
Increased—M2
M1 & M2 Mφ subsets (THP-1 cell line) [103]
[104]
Secreted Protein +/− IL-6 M1 Mφs
+/− IL-8/TNFα
M1 & M2 Mφ subsets (THP-1) [103]
[104]
SCFA-butyrate Suppression of IL-12 & augmentation of IL-10 Human monocytes [105]
SCFA-butyrate Decreased TNFα
Increased IL-10
M1 & M2 Mφ
subsets (THP-1)
[106]
L. helveticus DSM13137 L. rhamnosus GG S. thermophilus THS B. breve DSM13692 Increased IL-10:IL-12 ratios
Induced SOCS3 (IL-10 & p38 MAPK-dependent)
Human Mφs
GM-CSF-PB monocytes
[91]
L. plantarum K8 KCTC10887BP LTA (pLTA) Suppression of LPS
Induced TNFα (pLTA suppn of ERK, JNK, p38 MAPK
phosphorylation, IκB degradation & TLR4. Induction of IRAK-M.
THP-1 & U937 pro-monocytes
Murine sepsis model L929-BMM Balb/c
[96]
L. plantarum KCTC10887BP LTA (pLTA) Suppression of S. aureus LTA (aLTA) induced TNFα
pLTA suppresses Myd88, NFκB & MAPKs. Antagonises aLTA.
THP-1 pro-monocytes [97]
L. plantarum KCTC10887BP LTA (pLTA) Suppression of S. flexneri PGN
Induced inflammation (TNFα, IL-1β). Toln decreases NOD2; pLTA cross Toln Flex PGN
THP-1 pro-monocytes [98]
B. breve ATCC15700 B. longum ATCC15697 Enterococcus faecalis ATCC19433 Differential modulation of TNFα, IL-1β, IL-12p40 mRNA. Decreased IκB phosphorylation and induction of SOCS-1, -3. RAW264.7 murine Mφs
LPS-stimulated
[100]
LAB LTA
L. plantarum ATCC14917T L.casei YIT9029
Regulate TLR2-dependent
ERK mediated IL-12/IL-10 axis: LP high IL-10/IL-12, LC low IL-10/IL-12.
Murine peritoneal Mφs Balb/c [107]
L. rhamnosus GR1 & GG G-CSF-mediated inhibition of JNK: Suppression of TNFα Murine immort peritoneal & BMM C57Bl/6 Human THP-1s [89]
ProB DNA L. casei & B.breve Induction of IL-1, IL-10 & IL-6 Human PBMCs [108]
L. paracasei Cultech TLR2-dependent up-regulation of negative regulators of NFκB Human PBMCs & PMA-THP-1 cells. [109]
L. reuteri ATCC PTA 6475 CF48-3A & ATCC55730 conditioned medium Suppression of LPS-induced TNFα & MCP-1 via inhibition of MAPK-driven cJun/AP-1actn THP-1 cells, MonoMac-6 cells, CD Mφs [99]

Probiotics differentially modulate macrophage responses via activation of distinct pathogen sensing signaling pathways in a strain-dependent manner. Observations presented include a range of strains of bifidobacteria, lactobacilli, and streptococci and enterococci and the modulatory effect of probiotic DNA, conditioned medium, cell wall lipoteichoic acid (LTA) and the short-chain fatty acid (SCFA) metabolite, butyrate. Effector responses to probiotic introduction (and their products) are indicated as modulation of inflammation, pathogen sensing, cytokine production and their linkage to effects on signaling molecules and pathways. These observations have been recorded for a range of macrophage studies using distinct primary cells, cell lines and ex vivo models indicated.