• BMB Reports
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• v.49 no.6
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• pp.311-318
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• 2016

Innate immune responses are primary, relatively limited, and specific responses to numerous pathogens and toxic molecules. Protein expression involved in these innate responses must be tightly regulated at both transcriptional level and post-transcriptional level to avoid the development of excessive inflammation that can be potentially harmful to the host. MicroRNAs are small noncoding RNAs (∼22 nucleotides [nts]) that participate in the regulation of numerous physiological responses by targeting specific messenger RNAs to suppress their translation. Recent work has shown that several negative regulators of transcription including microRNAs play important roles in inhibiting the exacerbation of inflammatory responses and in the maintenance of immunological homeostasis. This emerging research area will provide new insights on how microRNAs regulate innate immune signaling. It might show that dysregulation of microRNA synthesis is associated with the pathogenesis of inflammatory and infectious diseases. In this review, we focused on miR-146 and miR-125 and described the roles these miRNAs in modulating innate immune signaling. These microRNAs can control inflammatory responses and the outcomes of pathogenic infections.

• Journal of Life Science
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• v.29 no.7
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• pp.817-823
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• 2019

Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.

• Archives of Pharmacal Research
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• v.15 no.1
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• pp.20-29
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• 1992

Effects of squalene on cellular and non-specific immune responses and antitumor activity in mice were investigated. Cellular and non-specific immunological assay parameters adopted in the present study were delayed-type hypersensitivity reaction and resette forming cells (RFC) for cellular immunity, activities of natural killer (NK) cells and phagocyte for non-specific immunity. Squalene resulted in marked increases of cellular and non-specific immune functions and enhancement of host resistance to tumor challenge in dose-dependent manner.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.7
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• pp.916-923
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• 2010

We report nutritional physiology and non-specific immune responses of vitamin E in parrot fish for the first time. This study aimed to investigate the essentiality and requirements in diets based on growth performances, non-specific immune responses and a challenge test against Vibrio angullarum. Six casein-gelatin based semi-purified diets were formulated to contain six graded levels of DL-${\alpha}$-tocopheryl acetate (${\alpha}$-TA) at 0, 25, 50, 75, 100 and 500 mg/kg diet (designated as E0, E25, E50, E75, E100 and E500, respectively) and fed to triplicate groups of juvenile parrot fish for 12 weeks. The analyzed dietary concentrations of vitamin E were 0, 38, 53, 87, 119 and 538 mg/kg diet for E0, E25, E50, E75, E100 and E500, respectively. At the end of the feeding trial, growth performance and feed utilization of fish fed the E25 were significantly higher compared to that of fish fed the other diets. Liver ${\alpha}$-tocopherol concentration was significantly increased with an increase in dietary ${\alpha}$-TA in a dose dependent manner. No apparent clinical signs of vitamin E deficiency and mortality were observed in fish fed the basal diet for 12 weeks. Among the immune responses assayed, phagocytic (NBT assay) and myeloperoxidase activities were significantly increased with increment of dietary ${\alpha}$-TA levels. During the challenge test with V. anguillarum, E75, E100, and E500 diets resulted in higher survivals than E0, E25 and E50 diets. The findings of this study suggest that parrot fish require exogenous vitamin E and the optimum dietary level could be approximately 38 mg ${\alpha}$-TA/kg diet for normal growth and physiology. Dietary ${\alpha}$-TA concentration over 500 mg/kg could be required to enhance the nonspecific immune responses and improve the resistance of juvenile parrot fish against V. anguillarum.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.73-82
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• 2015

Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.169-178
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• 2009

DNA immunization induces B and T cell responses to various pathogens and tumors. However, these responses are known to be relatively weak and often transient. Thus, novel strategies are necessary for enhancing immune responses induced by DNA immunization. Here, we demonstrated that co-immunization of influenza virus nucleoprotein (NP) gene significantly enhances humoral and cell-mediated responses to codelivered antigens in mice. We also found that NP DNA coimmunization augments in vivo proliferation of adoptively transferred antigen-specific CD4 and CD8 T cells, which enhanced protective immunity against tumor challenge. Our results suggest that NP DNA can serve as a novel genetic adjuvant in cocktail DNA vaccination.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.249-256
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• 2013

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

• Molecules and Cells
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• v.27 no.2
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• pp.243-250
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• 2009

Recent studies suggest a novel role of $HIF-1{\alpha}$ under nonhypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers $HIF-1{\alpha}$ activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of $HIF-1{\alpha}$ protein level as well as the increase in $HIF-1{\alpha}$ target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated $HIF-1{\alpha}$ knock-down. Interestingly, $HIF-1{\alpha}$ knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that $HIF-1{\alpha}$ activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.

• Parasites, Hosts and Diseases
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• v.50 no.4
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• pp.281-286
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• 2012

Helminthic infections afflict over 1.5 billion people worldwide, while Mycobacterium tuberculosis infects one third of the world's population, resulting in 2 million deaths per year. Although tuberculosis and helminthic infections coexist in many parts of the world, and it has been demonstrated that the T-helper 2 and T-regulatory cell responses elicited by helminths can affect the ability of the host to control mycobacterial infection, it is still unclear whether helminth infections in fact affect tuberculosis disease. In this review article, current progress in the knowledge about the immunomodulation induced by helminths to diminish the protective immune responses to bacille Calmette-Guerin vaccination is reviewed, and the knowledge about the types of immune responses modulated by helminths and the consequences for tuberculosis are summarized. In addition, recent data supporting the significant reduction of both M. tuberculosis antigen-specific Toll-like receptor (TLR) 2 and TLR9 expression, and pro-inflammatory cytokine responses to TLR2 and TLR9 ligands in individuals with M. tuberculosis and helminth co-infection were discussed. This examination will allow to improve understanding of the immune responses to mycobacterial infection and also be of great relevance in combating human tuberculosis.

• IMMUNE NETWORK
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• v.2 no.2
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• pp.65-71
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• 2002

The immunological mechanism of the responses to ultraviolet (UV) B radiation in mouse models were investigated by the suppression of contact hypersensitivity (CHS) and delayed type hypersensitivity (DTH), and susceptibility to infection. However, there are some differences in immune suppression according to the different models as well as the irradiation protocols. Therefore, this review focused on the differences in the suppressive effects on CHS and DTH, and susceptibility to infection in relation to the different in vivo models. Recent advances in cytokine knockout mice experiments have the reexamination of the role of the critical cytokines in UVB-induced immune suppression, which was investigated previously by blocking antibodies. The characteristics of the suppressor cells responsible for UVB-induced tolerance were determined. The subcellular mechanism of UVB-induced immune suppression was also explained by the induction of apoptotic cells through the Fas and Fas-ligand interaction. The phagocytosis of the apoptotic cells is believed to induce the production of the immune suppressive cytokine like interleukin-10 by macrophages. Therefore, the therapeutic UVB response to a skin disease, such as psoriasis, by the depletion of infiltrating T cells could be considered in the extension line of apoptosis and immune suppression.