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Shida et al (2009) Induction of interleukin-12 by Lactobacillus strains having a rigid cell wall resistant to intracellular digestion.

Shida et al (2009) Induction of interleukin-12 by Lactobacillus strains having a rigid cell wall resistant to intracellular digestion.


Shida K, Kiyoshima-Shibata, Kaji R, Nagaoka M, Nanno M (2009) Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms. Immunology 128 (suppl 1): e858-e869.


Lactobacilli with rigid cell walls resistant to intracellular digestion such as Lactobacillus casei Shirota (LcS) strongly stimulate macrophages to produce high levels of interleukin -12 (IL-12). This study continued the research into this, by comparing the effects of whole cells and cell wall components of other lactobacilli with easily digestible cell walls, on the LcS-induced production of IL-12 by macrophages and investigating the possible underlying mechanisms.


The study involved in vitro testing of mouse peritoneal macrophages with whole cells (heat-killed) and intact cell walls of LcS, L. johnsonii JCM 2012 and L. plantarum ATCC 14917, and purified peptidoglycan from Staphylococcus aureus

This included analysis of light and confocal laser scanning microscopy of macrophage intracellular digestion of the bacteria and their cell wall preparations, flow cytometry of the phagocytosis, treatment of the heat-killed bacteria or their cell wall components with N-acetylmuramidase (an enzyme that digests cell walls) and sodium dodecyl sulphate (an ionic detergent that can dissolve protoplasts); macrophage IL-12 mRNA expression and enzyme-linked immunosorbent assays (ELISA) to detect various cytokines.


Whole cells and intact cells walls of the L. johnsonii and L. plantarum strains (whose cell walls are easily digested by the macrophages) only weakly induced macrophage production of IL-12, and inhibited LcS induced IL-12 production.

The intact cell wall of LcS was resistant to intracellular digestion and did not inhibit LcS-induced IL-12 production. However, when the polysaccharide component was removed from the LcS intact cell wall preparations to leave just the intact peptidoglycan moiety, this was sensitive to intracellular digestion and also inhibited LcS-induced IL-12 production.

Peptidoglycan preparations from strains of L. johnsonii, L. plantarum as well as Staphylococcus aureus also inhibited LcS-induced IL-12 production. Lactobacilli peptidoglycan preparations prevented LcS-induced expression of IL-12p40 but not IL-12p35 mRNA.

Tests with macrophages unable to express the pattern recognition receptor TLR-2 (Toll-like receptor), showed that recognition of peptidoglycan by TLR2 was an important part of the process that resulted in inhibition of IL-12 production.

NOD2 (nucleotide-blinding oligomerization domain 2) is a cytoplasmic pattern recognition receptor able to recognise digested peptidoglycan products. A subunit of peptidoglycan (muramyl dipeptide) was recognised by NOD2, and inhibited LcS-induced IL-12 production.


These data show that easily digested bacteria and peptidoglycan can suppress IL-12 production via TLR2 and NOD2 pattern recognition receptors. Thus, the authors speculated that production of IL-12 in the gut by certain bacteria might be downregulated by the combined effects of peptidoglycan from various bacteria of the commensal flora that are easily digested. This may be a mechanism that helps maintain intestinal homeostasis.

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