• Microbiology and Biotechnology Letters
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• v.47 no.1
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• pp.132-138
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• 2019

Among several marine-derived microorganisms isolated from the coast of Jeju Island that had antimicrobial activity against fish disease pathogens, Bacillus subtilis MD-02 was tested for its dietary effect on the innate immune response and disease resistance of olive flounder. Strain MD-02 was fed to the olive flounder at a concentration of $1.2{\times}10^4$, $1.2{\times}10^6$, or $1.2{\times}10^8CFU/100g$, respectively. Consequently, the hematocrit was higher in these three groups than that in the control group at 4 weeks, and the aspartate aminotransferase and alanine aminotransferase levels were decreased in the $1.2{\times}10^8$ and $1.2{\times}10^4CFU/100$ groups compared with the control group levels. The amylase activity and total protein were significantly increased in the $1.2{\times}10^4CFU/100g$ group at 3 weeks. The innate immune response, determined from the lysozyme and macrophage activities, was higher in the $1.2{\times}10^8CFU/100g$ group than in the control group. In addition, treatment of the olive flounders with Streptococcus parauberis at $1.2{\times}10^6CFU/ml$ confirmed the mortality rate, which was 100% in the control group and 40-60% in the groups fed B. subtilis MD-02, indicating that the fish had resistance to fish disease pathogens. Therefore, it was confirmed that when fed MD-02, olive flounder builds an innate immune response and acquires resistance to fish disease pathogens, indicating that B. subtilis MD-02 can be developed as a beneficial feed additive.

• Proceedings of the Microbiological Society of Korea Conference
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• 2008.05a
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• pp.23-25
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• 2008

Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

• Fisheries and Aquatic Sciences
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• v.25 no.4
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• pp.243-249
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• 2022

Bacillus SW1-1 is a probiotic isolated from shrimp intestines. We investigated the effects of Bacillus SW1-1 coated diets on the growth, feed utilization, innate immunity, hematological parameters and resistance to Edwardsiella tarda in olive flounder (Paralichthys olivaceus). A commercial diet was used as the control (AP0) and two other diets were prepared by coating 0.25% (AP25) or 0.50% (AP50) probiotic powder which contains 1.0 × 10⁷ CFU/g Bacillus SW1-1. Four replicate groups of olive flounder (153 ± 2 g) were fed one of the diets for 12 weeks. Growth performance and feed utilization of the fish were not significantly affected by the dietary Bacillus SW1-1. After the challenge with E. tarda, AP50 group showed significantly higher survival than AP0 and AP25 groups. Innate immunity and anti-oxidant capacity of the fish were not significantly affected after the feeding trial. However, after the E. tarda challenge, the innate immune parameters (immunoglobulin, lysozyme and anti-protease) were significantly improved in fish fed AP25 and AP50 diets compared to those in fish fed AP0 diet. After the challenge test, significantly lower glucose level was observed in AP50 group compared to AP0 group. These results indicate that dietary supplementation of Bacillus SW1-1 could increase the disease resistance of olive flounder against E. tarda infection. The optimum coating levels of Bacillus SW1-1 needs to be further elucidated.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.3
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• pp.89-98
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• 2023

Background: The regulation of maternal immunity is critical for the establishment and maintenance of successful pregnancy. Among many cell types regulating the immune system, innate lymphoid cells (ILCs) are known to play an important role in innate immunity. Although some reports show that ILCs are present at the maternalconceptus interface in humans and mice, the expression and function of ILCs in the endometrium have not been studied in pigs. Methods: Thus, we determined the expression, localization, and regulation of ILC markers, CD127 (a common marker for ILCs), BCL11B (a ILC2 marker), and RORC (a ILC3 marker) at the maternal-conceptus interface in pigs. Results: The expression of BCL11B and RORC, but not CD127, in the endometrium changed during pregnancy in a stage-specific manner and the expression of CD127, BCL11B, and RORC was greatest on Day 15 during pregnancy. CD127, BCL11B, and RORC were also expressed in conceptus tissues during early pregnancy and in chorioallantoic tissues during the later stage of pregnancy. BCL11B and RORC proteins were localized to specific cells in endometrial stroma. The expression of CD127 and BCL11B, but not RORC, was increased by the increasing doses of interferon-γ (IFNG) in endometrial explants. Conclusions: These results suggest that ILCs present at the maternal-conceptus interface may play a role in the establishment and maintenance of pregnancy by regulating the innate immunity in pigs.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.126-133
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• 2016

Unlike conventional T cells, innate CD8 T cells develop a memory-like phenotype in the thymus and immediately respond upon antigen stimulation, similar to memory T cells. The development of innate CD8 T cells in the thymus is known to require IL-4, which upregulates Eomesodermin (Eomes). These features are similar to that of virtual memory CD8 T cells and IL-4-induced memory-like CD8 T cells generated in the peripheral tissues. However, the relationship between these cell types has not been clearly documented. In the present study, IL-4-induced memory-like CD8 T cells generated in the peripheral tissues were compared with innate CD8 T cells in terms of phenotype and function. When an IL-4/anti-IL-4 antibody complex (IL-4C) was injected into C57BL/6 mice daily for 7 days, the Eomes^hiCXCR3⁺ CD8 T cell population was markedly increased in the peripheral lymphoid organs and blood. These cells were generated from naïve CD8 T cells or accumulated via the expansion of pre-existing CD44^hiCXCR3⁺ CD8 T cells. Initially, the majority of these CXCR3⁺ CD8 T cells expressed low levels of CD44, which was followed by the conversion to the CD44^hi phenotype. This conversion was associated with the acquisition of enhanced effector function. After discontinuation of IL-4C treatment, Eomes expression levels gradually decreased in CXCR3⁺ CD8 T cells. Taken together, the results of this study demonstrate that IL-4-induced memory-like CD8 T cells generated in the peripheral lymphoid tissues are phenotypically and functionally similar to the innate CD8 T cells generated in the thymus.

• IMMUNE NETWORK
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• v.8 no.4
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• pp.124-129
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• 2008

Background: The immunomodulatory effects of Korean mistletoe (Viscum album Coloratum) on the innate immune responses of eel (Anguilla japonica) were studied. Methods: Mistletoe, Freund’s complete adjuvant (FCA), or phosphate-buffered saline (PBS) as a control was injected into eel peritoneal cavities. Results: Nitroblue tetrazolium (NBT)-positive cells in the head kidney of eel were significantly augmented by the second day post-injection of mistletoe. Reactive oxygen intermediates (ROI) were more produced in mistletoe-injected fish kidney leucocytes than in FCA-injected ones. The level of lysozyme activity in the serum of fish 2 days after injection with mistletoe was also significantly higher than that in the serum of the control fish. The optimal concentration of mistletoe in inducing the highest serum lysozyme activity was revealed to 500${\mu}$g/200 g of fish. In phagocytic activity assay, mistletoe-sensitized eel kidney phagocytes captured more zymosan than did the control fish. Conclusion: Korean mistletoe appeared to be a good activator of the non-specific immune responses of eel.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8445-8450
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• 2016

Background: Breast cancer is the most common neoplasm in women and the most frequent cause of death in those between 35 and 55 years of age. All multicellular organisms have an innate immune system, whereas the adaptive or 'acquired' immune system is restricted to vertebrates. This study focused on the effect of conditioned medium isolated from cultured breast cancer cells on NB4 neutrophil-like cells. Materials and Methods: In the current study neutrophil-like NB4 cells were incubated with MCF-7 cell-conditioned medium. After 6 h incubation the intracellular receptor TLR2, was analyzed. Results: The results revealed that MCF-7 cell-conditioned medium elicited expression of TLR2 in NB4 cells. Conclusions: This treatment would result in the production of particular stimulants (i.e. soluble cytokines), eliciting the expression of immune system receptors. Furthermore, the flow cytometry results demonstrated that MCF-7 cell-conditioned medium elicited an effect on TLR2 intracellular receptors.

• IMMUNE NETWORK
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• v.9 no.2
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• pp.41-45
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• 2009

Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300). MAIR is a multigene family consisting of nine genes on a small segment of mouse chromosome 11. MAIR family receptors are preferentially expressed on myeloid cells, including macrophages, dendritic cells, granulocytes, and bone-marrow-derived cultured mast cells, and a subset of B cells and regulate activation of these cells. Thus, MAIR plays an important role in innate immunity mediated by myeloid cells.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.115-119
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• 2010

Lymphoid tissue inducer (LTi) cells have been characterized in mouse as a key cell when secondary lymphoid tissues are organized during development and memory T cells are formed after birth. In addition to their involvement in adaptive immune responses, recent studies show that they contribute to innate immune responses by producing large amount of interleukin (IL)-22 against microbial attack. Here, we compare IL-22-producing LTi and LTi-like cells in human and mouse and discuss their heterogeneity in different tissues.

• Clinical and Experimental Pediatrics
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• v.58 no.7
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• pp.239-244
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• 2015

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.