Immunostimulating Properties of Intragastrically AdministeredAcetobacter-Derived Soluble Branched (1,4)-β-d-Glucans Decrease Murine Susceptibility toListeria monocytogenes

Abstract

We previously found that AC-1, an extracellular polysaccharide, produced by Acetobacter xylinum and composed of (1,4)-␤-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)-␤-D-glucan.

Host Genetics of Bordetella pertussis Infection in Mice: Significance of Toll-Like Receptor 4 in Genetic Susceptibility and Pathobiology

“…In C3H/HeJ mice, however, there was very little production of IL-1␤, and little production of TNF-␣, and no IFN-␥ production. Although Higgins et al (11) suggested a role for Tlr4 in inhibiting Th1 responses by activating IL-10 production, our results indicate that Tlr4 engagement is essential not only for the innate response but also for stimulation of the ensuing Th1 response, which is in line with other reports (7,12,18,22). Functional Tlr4 may be required for the production of IL-10, which is associated with limiting the inflammatory pathology (11).…”

“…IL-1␤, TNF-␣, and IFN-␥ production were determined in supernatants of splenocytes isolated at various days after infection from B. pertussis-infected A/J and C3H/HeJ mice after 3 days of ex vivo restimulation with heatinactivated B. pertussis or ConA. Because Tlr4 engagement also modulates the adaptive Th1 immune response (7,12,18,22), IFN-␥ was taken as a parameter of the acquired immune response.…”

Polysaccharide biological response modifiers

“…Cellulomonas flavigena KU also produces curdlan-type (␤-1,3-glucan) exopolysaccharide [37]. EP produced by Acetobacter xylinum is named AC-1, which is composed of ␤-1,4-d-glucan with branches of glucosyl residues [8]. EP produced by Pseudomonas aeruginosa is named mannuronan and is a polymer of ␤-1,4-linked d-mannuronate [38].…”

“…Bacterial polysaccharide BRMs can be capsular polysaccharides [1][2][3][4] and exopolysaccharide [5][6][7][8]. The bacterial membrane and cell wall are the major sources of polysaccharide BRMs of bacterial origin.…”

Protective Effect of Beta Glucan on Pulmonary Aspergillosis Model in Neutropenic Rats

“…They fo und that Ace to bac ter-de ri ved so lub le branc hed (1,4)-be ta-D-glu can en han ced an ti bac teri al ac ti vity vi a in ce a sing IL-12 le vels thro ugh Tollli ke re cep tor 4, and aug men ting Th1/Tc1 res pon ses. 31 In two do ub le-blind pla ce bo-con trolled ran do mi sed pha se II tri als by Ba bi ne a u et al, the pro tec ti ve ef fect of be ta-D glu cans aga inst postope ra ti ve in fec ti ons was al so ob ser ved in high risk sur gi cal pa ti ents. 32,33 They in di ca ted that pa ti ents who re ce i ved poly-(1-6)-be ta-D-glu cop yra nosyl-(1-3)-be ta-D glu cop yra no se glu can had sig ni ficantly fe wer in fec ti o us comp li ca ti ons, dec re a sed in tra ve no us an ti bi o tic re qu i re ment and shor ter inten si ve ca re unit length of stay.…”