Immunostimulating properties of intragastrically administered Acetobacter-derived soluble branched (1,4)-beta-D-glucans decrease murine susceptibility to Listeria monocytogenes.
We previously found that AC-1, an extracellular polysaccharide, produced by Acetobacter xylinum and composed of (1,4)-beta-D-glucan with branches of glucosyl residues, showed a strong activity to induce production of interleukin-12 (IL-12) p40 and tumor necrosis factor alpha by macrophages in vitro via Toll-like receptor 4 (TLR-4) signaling. In the present study, we examined the effect of oral administration of AC-1 on protective immunity against Listeria monocytogenes. Mice were given AC-1 or phosphate-buffered saline (PBS) intragastrically 2 days before, on the day of, and 2 days after an intraperitoneal inoculation of L. monocytogenes. The survival rate of AC-1-treated mice was significantly improved and bacterial growth in AC-1-treated mice was severely retarded compared to those of PBS-treated mice after infection with L. monocytogenes. IL-12 p40 levels in serum and magnitudes of CD4+ Th1 and CD8+ Tc1 responses against Listeria antigen were significantly higher in AC-1-treated mice than in PBS-treated mice. The effect of AC-1 on antilisterial activity was diminished in C3H/HeJ mice carrying mutated TLR-4. Thus, AC-1, a potent IL-12 inducer through TLR-4, enhanced protective immunity against L. monocytogenes via augmentation of Th1 responses. These results suggest that infectious processes driven by intracellular microorganisms could be prevented to develop by the (1,4)-beta-D-glucan.
Li
Wei
W
Division of Host Defense, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Yajima
Toshiki
T
Saito
Kimika
K
Nishimura
Hitoshi
H
Fushimi
Takashi
T
Ohshima
Yoshifumi
Y
Tsukamoto
Yoshinori
Y
Yoshikai
Yasunobu
Y
D000091:Acetobacter / Q000737:chemistry*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004198:Disease Susceptibility; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000502:physiology; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D047071:beta-Glucans / Q000008:administration & dosage / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D018664:Interleukin-12; D007371:Interferon-gamma