Role of lactic acid microbes in defense against infection: Exopolysaccharide produced by Leuconostoc mesenteroides enhances antigen-specific IgA secretion

Antigen-specific immunoglobulin A (IgA) plays a salient role in host defense against mucosal infection. We reported earlier that exopolysaccharide (EPS) produced by probiotic Leuconostoc mesenteroides strain NTM048 can enhance mucosal IgA production in mice. However, the capability of enhancing antigen-specific IgA production remains unclear.

Here, Chiaki Matsuzaki of Ishikawa Prefectural University and colleagues in Japan used BALB/c mice to investigate EPS effects on antigen-specific IgA production and the molecular mechanisms underlying those effects. The EPS (100 µg) was administrated with an antigen (ovalbumin, 5 µg) intranasally four times. Blood samples, nasal washes, and bronchoalveolar lavage fluid (BALF) samples were examined for antigen-specific antibody responses. EPS caused increased secretion of antigen-specific IgA in the nasal wash and the serum. The secretions of antigen-specific IgG in the BALF and the serum were also increased. These results indicate that EPS administration enhanced mucosal and systemic immune responses to an antigen.

The immunostimulatory effect of EPS on dendritic cells (DCs) was studied clarify the underlying mechanisms. Notably, DCs are a family of highly specialized antigen-presenting cells that are potent activators of naïve T cells and regarded as important initiators of primary immune responses. The researchers used murine bone marrow-derived DCs (BMDCs) to evaluate the immunostimulatory capabilities of the EPS. BMDCs were cultured with stimulation by 100 µg/mL of EPS. The expression of the genes of the mediators of mucosal immunity was analyzed. After 3 h stimulation, the gene expressions of IL-6, IL-12, IL-10, and retinal dehydrogenase 2 (RALDH2), which catalyze to synthesize retinoic acid (RA) from retinol, increased significantly. The increased protein production of these upregulated genes was also confirmed by enzyme-linked immunosorbent assay and flow cytometric aldehyde dehydrogenase assay (for RALDH2).

The synthesis of RA and IL-10 by intestinal DCs regulates affinity maturation of IgA. They are therefore crucially important for antigen specificity. RA, IL-6, and T-cell-produced IL-5 synergistically enhance class switching to IgA in B cells. IL-12 was recently reported as contributing to driving follicular helper T cell differentiation, which is necessary for B cells to produce antigen-specific IgA. The EPS is expected to regulate IgA-specificity through education of DCs to produce IL-6, IL-10, IL-12, and RA.

Reference
The 7th Beneficial Microbes Conference

Exopolysaccharide produced by Leuconostoc mesenteroides strain NTM048 enhances antigen-specific IgA secretion
C. Matsuzaki1, C. Takagaki1,2, Y. Higashimura3, Y. Nakashima1, K. Hosomi2, J. Kunisawa2, K. Yamamoto1, K. Hisa4

1 Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Japan
2 Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition, Japan
3 Department of Food Science, Ishikawa Prefectural University, Japan
4 Nitto Pharmaceutical Industries, Ltd., Japan

Further information
The 7th Beneficial Microbes Conference
https://www.beneficialmicrobes2018.org/
Amsterdam, Netherlands, 26-28 November 2018

Caption: Specific antibody responses in mice after intranasal immunization with OVA + NTM048 EPS. (a) Time schedules for intranasal vaccination (IN) and the sampling of serum, bronchoalveolar lavage fluids (BALF), and nasal washes. Each dose contained 5 μg of OVA plus 100 μg of EPS or 1 μg of CT (each group, n = 6). On day 42, the OVA-specific antibodies in BALF, nasal washes (b) and the serum (c) were measured. Data represents one of two independent experiments with similar results. *P < 0.05, **P < 0.01 (Dunnett’s multiple comparison test).