Stress, Nutrition, and Intestinal Immune Responses in Pigs - A Review

Lee, In Kyu,Kye, Yoon Chul,Kim, Girak,Kim, Han Wool,Gu, Min Jeong,Umboh, Johnny,Maaruf, Kartini,Kim, Sung Woo,Yun, Cheol-Heui Asian Australasian Association of Animal Productio 2016 Animal Bioscience Vol.29 No.8

Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles.

Intranasal immunization with pneumococcal surface protein A in the presence of nanoparticle forming polysorbitol transporter adjuvant induces protective immunity against the <i>Streptococcus pneumoniae</i> infection

Kye, Yoon-Chul,Park, Sung-Moo,Shim, Byoung-Shik,Firdous, Jannatul,Kim, Girak,Kim, Han Wool,Ju, Young-Jun,Kim, Cheol Gyun,Cho, Chong-Su,Kim, Dong Wook,Cho, Jae Ho,Song, Man Ki,Han, Seung Hyun,Yun, Cheo Elsevier 2019 Acta Biomaterialia: structure-property-function re Vol.90 No.-

<P><B>Abstract</B></P> <P>Developing effective mucosal subunit vaccine for the <I>Streptococcus pneumoniae</I> has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the <I>Streptococcus pneumoniae</I>. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against <I>S. pneumoniae</I> challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against <I>S. pneumoniae</I> infection.</P> <P><B>State of Significance</B></P> <P>In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against <I>Streptococcus pneumoniae</I> lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Distinct pattern of immune tolerance in dendritic cells treated with lipopolysaccharide or lipoteichoic acid

Yoon, Hyo Shin,Kim, Girak,Ju, Young Jun,Cheon, In Su,Hong, Sun Woong,Kim, Dong Wook,Park, Byung-Chul,Han, Seung Hyun,Yun, Cheol-Heui 3M Company 2017 Molecular immunology Vol.91 No.-

<P>A transient hyporesponsiveness period appeared when DCs were treated repeatedly with LTA or LPS showing a distinctive pattern. Intriguingly, LPS exposure induced cross tolerance to LTA while LTA exposure did not to LPS, implicating that a distinct signaling components are involved in response to LTA. Collectively, a distinct immune regulation appeared to be responsible for the LPS- and LTA-induced tolerance on cytoldne production, expression of surface markers and intracellular proteins.</P>

H9N2-specific IgG and CD4+ CD25+ T cells in broilers fed a diet supplemented with organic acids

Lee, In Kyu,Bae, Suhan,Gu, Min Jeong,You, Sun Jong,Kim, Girak,Park, Sung-Moo,Jeung, Woon-Hee,Ko, Kwang Hyun,Cho, Kyung Jin,Kang, Jung Sun,Yun, Cheol-Heui Elsevier 2017 Poultry science Vol.96 No.5

<P>Organic acids have long been known for their beneficial effects on growth performance in domestic animals. However, their impact on immune responses against viral antigens in chickens is unclear. The present study aimed to investigate immunological parameters in broilers immunized with a H9N2 vaccine and/or fed a diet containing organic acids (citric, formic, and lactic acids). We allotted 1-day-old broilers into 4 groups: control (C), fed a diet supplemented with organic acids (O), administered a H9N2 vaccine (V), and fed a diet supplemented with organic acids and administered a H9N2 vaccine (OV). Blood and spleen samples were taken at 2, 7 and 14 d post vaccination (DPV). At 14 DPV, total and H9N2-specific IgG levels were significantly lower in the OV group than in the V group. However, it was intriguing to observe that at 2 DPV, the percentage of CD4(+) CD25(+) T cells was significantly higher in the OV group than in the other groups, indicating the potential induction of regulatory T cells by organic acids. In contrast, at 2 DPV, the percentage of CD4(+) CD28(+) T cells were significantly lower in the OV group than in the other groups, suggesting that CD28 molecules are down-regulated by the treatment. The expression of CD28 on CD4(+) T cells, up-regulated by the stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin (Iono), was inhibited upon organic acid treatment in OV group. In addition, the proliferation of lymphocytes, stimulated with formalin-inactivated H9N2, was significantly higher in the V group than in the OV group. Alpha 1-acid glycoprotein (AGP) production was significantly lower in the OV group than in the V group, suggesting that the organic acids inhibited the inflammation caused by the vaccination. Overall, induction of regulatory CD4(+) CD25(+) T cells, coinciding with the decrease of H9N2-specific antibodies, was observed in broilers fed organic acids.</P>

A Bacterial Metabolite, Compound K, Induces Programmed Necrosis in MCF-7 Cells via GSK3β

( Chae Won Kwak ),( Young Min Son ),( Min Jeong Gu ),( Girak Kim ),( In Kyu Lee ),( Yoon Chul Kye ),( Han Wool Kim ),( Ki Duk Song ),( Hyuk Chu ),( Byung Chul Park ),( Hak Kyo Lee ),( Deok Chun Yang ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.7

Ginsenosides, the major active component of ginseng, are traditionally used to treat various diseases, including cancer, inflammation, and obesity. Among these, compound K (CK), an intestinal bacterial metabolite of the ginsenosides Rb1, Rb2, and Rc from Bacteroides JY-6, is reported to inhibit cancer cell growth by inducing cell-cycle arrest or cell death, including apoptosis and necrosis. However, the precise effect of CK on breast cancer cells remains unclear. MCF-7 cells were treated with CK (0-70 μM) for 24 or 48 h. Cell proliferation and death were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Changes in downstream signaling molecules involved in cell death, including glycogen synthase kinase 3β (GSK3β), GSK3β, β-catenin, and cyclin D1, were analyzed by western blot assay. To block GSK3β signaling, MCF-7 cells were pretreated with GSK3β inhibitors 1 h prior to CK treatment. Cell death and the expression of β-catenin and cyclin D1 were then examined. CK dose- and time-dependently inhibited MCF-7 cell proliferation. Interestingly, CK induced programmed necrosis, but not apoptosis, via the GSK3β signaling pathway in MCF-7 cells. CK inhibited GSK3β phosphorylation, thereby suppressing the expression of β-catenin and cyclin D1. Our results suggest that CK induces programmed necrosis in MCF-7 breast cancer cells via the GSK3β signaling pathway.

Systemic administration of RANKL overcomes the bottleneck of oral vaccine delivery through microfold cells in ileum

Maharjan, Sushila,Singh, Bijay,Jiang, Tao,Yoon, So-Yeon,Li, Hui-Shan,Kim, Girak,Gu, Min Jeong,Kim, Soo Ji,Park, Ok-Jin,Han, Seung Hyun,Kang, Sang-Kee,Yun, Cheol-Heui,Choi, Yun-Jaie,Cho, Chong-Su Elsevier 2016 Biomaterials Vol.84 No.-

<P><B>Abstract</B></P> <P>A successful delivery of antigen through oral route requires to overcome several barriers, such as enzymatic barrier of gastrointestinal tract and epithelial barrier that constitutes of microfold cells (M cells) for antigen uptake. Although each barrier represents a critical step in determining the final efficiency of antigen delivery, the transcytosis of antigen by M cells in the follicle-associated epithelium (FAE) to Peyer's patches appears to be a major bottleneck. Considering the systemic administration of receptor activator of nuclear factor (NF)-ĸB ligand (RANKL) induces differentiation of receptor activator of nuclear factor (NF)-ĸB (RANK)-expressing enterocytes into M cells, here, we illustrated a promising approach of antigen delivery using full length transmembrane RANKL (mRANKL). The results showed that the intraperitoneal injection of mRANKL increased the population of dendritic cells and macrophages in mesenteric lymph nodes and spleen. Subsequently, systemic administration of mRANKL resulted in significantly higher number of functional GP2<SUP>+</SUP> M cells leading higher transcytosis of fluorescent beads through them. To corroborate the effect of mRANKL in antigen delivery through M cells, we orally delivered microparticulate antigen to mice treated with mRANKL. Oral immunization induced strong protective IgA and systemic IgG antibody responses against orally delivered antigen in mRANKL-treated mice. The higher antibody responses are attributed to the higher transcytosis of antigens through M cells. Ultimately, the higher memory B cells and effector memory CD4 T cells after oral immunization in RANKL-treated mice confirmed potency of RANKL-mediated antigen delivery. To the best of our knowledge, this is the first study to demonstrate significant induction of mucosal and humoral immune responses to M cell targeted oral vaccines after the systemic administration of RANKL.</P>