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Modulation of Innate Immunity by lignin-Carbohydrate, a Novel TLR4 Ligand, Results in Augmentation of Mucosal IgA and Systemic IgG Production.

ABSTRACT: Previous study revealed that a specific lignin-carbohydrate preparation, named as lignin-rich enzyme lignin (LREL) derived from plant husk, is a novel toll-like receptor 4 ligand and shows a potent immune-stimulatory activity against dendritic cells (DCs) in vitro. In this report, we investigated immune-stimulatory activity of LREL in vivo. Single intraperitoneal (i.p.) or oral treatment of LREL elicited activation of systemic and mucosal DCs, which were accompanied by significant elevation of cell surface activation markers and ratio of IL-12p40 producing cells. In addition, LREL-fed mice showed not only mucosal DCs activation but also significant increase of IFN-?? CD4? T cells in mesenteric lymph node (MLN), respectively. We further examined the effect of LREL oral immunization in combination with ovalbumin (OVA) on the activation of acquired immune system. In LREL administered group, total mucosal IgA concentration was significantly increased, while antigen-specific immunoglobulin A (IgA) concentration was not changed between groups. On the other hand, both total and antigen-specific IgG concentrations in plasma were significantly increased in the LREL administered group. Taken together, oral treatment of LREL is able to affect mucosal and systemic antibodies induction and might be useful for effective immune-stimulatory functional foods and mucosal vaccine adjuvant.

SUBMITTER: Tsuji R

PROVIDER: S-EPMC5796014 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Modulation of Innate Immunity by lignin-Carbohydrate, a Novel TLR4 Ligand, Results in Augmentation of Mucosal IgA and Systemic IgG Production.

Tsuji Ryohei R Ikado Kumiko K Fujiwara Daisuke D

International journal of molecular sciences 20171226 1

Previous study revealed that a specific lignin-carbohydrate preparation, named as lignin-rich enzyme lignin (LREL) derived from plant husk, is a novel toll-like receptor 4 ligand and shows a potent immune-stimulatory activity against dendritic cells (DCs) in vitro. In this report, we investigated immune-stimulatory activity of LREL in vivo. Single intraperitoneal (i.p.) or oral treatment of LREL elicited activation of systemic and mucosal DCs, which were accompanied by significant elevation of c ...[more]

PMID: 29278400

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Project description:Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA)-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be particularly important for heterosubtypic immunity.

Project description:BackgroundThe interaction between nutrition and immunity plays a vital role in nutrient digestion, absorption, and metabolism during poultry production. Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity. However, the mechanisms by which gut microbes regulate this process remain unclear.MethodsWe compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers (AA (lower mucosal immunity) and Chinese native Wuliang Mountain Black-bone chickens (WLMB) (higher mucosal immunity) using 16S rDNA sequencing, transcriptomic analysis, and immunoglobulin A (IgA) antibody repertoire sequencing. We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production. Next, we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity. Finally, we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells (IECs) using in vitro experiments.ResultsWLMB performs stronger mucosal immunity than AA, including higher IgA levels, more diverse IgA antibody repertoire, and higher bacterial affinity. Bacteroides was identified as the key microbes related to the intestinal IgA response. Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA, polymeric immunoglobin receptor (PIgR), B cell-activating factor of the TNF family (BAFF), and activation-induced cytidine deaminase (AID) in the duodenum. Additionally, Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines, including interleukin (IL)-10, IL-4, BAFF, and transforming growth factor-beta (TGF-β), thus promoting IgA production in B cells by facilitating AID expression.ConclusionOur study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers. Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing next-generation probiotics for broiler production.

Dataset Information

Modulation of Innate Immunity by lignin-Carbohydrate, a Novel TLR4 Ligand, Results in Augmentation of Mucosal IgA and Systemic IgG Production.

Publications

Modulation of Innate Immunity by lignin-Carbohydrate, a Novel TLR4 Ligand, Results in Augmentation of Mucosal IgA and Systemic IgG Production.

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