Affiliation:
1. Yakult Central Institute for Microbiological Research, Yaho, Kunitachi, Tokyo 186-8650, Japan
Abstract
ABSTRACT
Although many
Lactobacillus
strains used as probiotics are believed to modulate host immune responses, the molecular natures of the components of such probiotic microorganisms directly involved in immune modulation process are largely unknown. We aimed to assess the function of polysaccharide moiety of the cell wall of
Lactobacillus casei
strain Shirota as a possible immune modulator which regulates cytokine production by macrophages. A gene survey of the genome sequence of
L. casei
Shirota hunted down a unique cluster of 10 genes, most of whose predicted amino acid sequences had similarities to various extents to known proteins involved in biosynthesis of extracellular or capsular polysaccharides from other lactic acid bacteria. Gene knockout mutants of eight genes from this cluster resulted in the loss of reactivity to
L. casei
Shirota-specific monoclonal antibody and extreme reduction of high-molecular-mass polysaccharides in the cell wall fraction, indicating that at least these genes are involved in biosynthesis of high-molecular-mass cell wall polysaccharides. By adding heat-killed mutant cells to mouse macrophage cell lines or to mouse spleen cells, the production of tumor necrosis factor alpha, interleukin-12 (IL-12), IL-10, and IL-6 was more stimulated than by wild-type cells. In addition, these mutants additively enhanced lipopolysaccharide-induced IL-6 production by RAW 264.7 mouse macrophage-like cells, while wild-type cells significantly suppressed the IL-6 production of RAW 264.7. Collectively, these results indicate that this cluster of genes of
L. casei
Shirota, which have been named
cps1A
,
cps1B
,
cps1C
,
cps1D
,
cps1E
,
cps1F
,
cps1G
, and
cps1J
, determine the synthesis of the high-molecular-mass polysaccharide moiety of the
L. casei
Shirota cell wall and that this polysaccharide moiety is the relevant immune modulator which may function to reduce excessive immune reactions during the activation of macrophages by
L. casei
Shirota.
Publisher
American Society for Microbiology
Subject
Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology
Cited by
123 articles.
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