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2 pages, 178 KiB

Open AccessEditorial

Innate–Acquired Linkage in Immunotherapy

by Tsukasa Seya

Cells 2023, 12(3), 371; https://doi.org/10.3390/cells12030371 - 19 Jan 2023

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Abstract

The evolution of the human species is the result of genetic variation [...] Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

Research

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18 pages, 5613 KiB

Open AccessArticle

TLR2 Signaling Pathway Combats Streptococcus uberis Infection by Inducing Mitochondrial Reactive Oxygen Species Production

by Bin Li, Zhixin Wan, Zhenglei Wang, Jiakun Zuo, Yuanyuan Xu, Xiangan Han, Vanhnaseng Phouthapane and Jinfeng Miao

Cells 2020, 9(2), 494; https://doi.org/10.3390/cells9020494 - 21 Feb 2020

Cited by 22 | Viewed by 3231

Abstract

Mastitis caused by Streptococcus uberis (S. uberis) is a common and difficult-to-cure clinical disease in dairy cows. In this study, the role of Toll-like receptors (TLRs) and TLR-mediated signaling pathways in mastitis caused by S. uberis was investigated using mouse models [...] Read more.

Mastitis caused by Streptococcus uberis (S. uberis) is a common and difficult-to-cure clinical disease in dairy cows. In this study, the role of Toll-like receptors (TLRs) and TLR-mediated signaling pathways in mastitis caused by S. uberis was investigated using mouse models and mammary epithelial cells (MECs). We used S. uberis to infect mammary glands of wild type, TLR2^−/− and TLR4^−/− mice and quantified the adaptor molecules in TLR signaling pathways, proinflammatory cytokines, tissue damage, and bacterial count. When compared with TLR4 deficiency, TLR2 deficiency induced more severe pathological changes through myeloid differentiation primary response 88 (MyD88)-mediated signaling pathways during S. uberis infection. In MECs, TLR2 detected S. uberis infection and induced mitochondrial reactive oxygen species (mROS) to assist host in controlling the secretion of inflammatory factors and the elimination of intracellular S. uberis. Our results demonstrated that TLR2-mediated mROS has a significant effect on S. uberis-induced host defense responses in mammary glands as well as in MECs. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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Review

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14 pages, 1160 KiB

Open AccessReview

Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement

by Tsukasa Seya, Megumi Tatematsu and Misako Matsumoto

Cells 2022, 11(24), 4006; https://doi.org/10.3390/cells11244006 - 11 Dec 2022

Cited by 4 | Viewed by 1828

Abstract

The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens and cancer cells have unique amino acid sequences and motifs (e.g., microbe-associated molecular patterns, MAMPs) that are recognized as “non-self” to [...] Read more.

The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens and cancer cells have unique amino acid sequences and motifs (e.g., microbe-associated molecular patterns, MAMPs) that are recognized as “non-self” to the host, immune enhancement is one strategy to eliminate invading cells. MAMPs contain nucleic acids specific or characteristic of the microbe and are potential candidates for immunostimulants or adjuvants. Adjuvants are included in many vaccines and are a way to boost immunity by deliberately administering them along with antigens. Although adjuvants are an important component of vaccines, it is difficult to evaluate their efficacy ex vivo and in vivo on their own (without antigens). In addition, inflammation induced by currently candidate adjuvants may cause adverse events, which is a hurdle to their approval as drugs. In addition, the lack of guidelines for evaluating the safety and efficacy of adjuvants in drug discovery research also makes regulatory approval difficult. Viral double-stranded (ds) RNA mimics have been reported as potent adjuvants, but the safety barrier remains unresolved. Here we present ARNAX, a noninflammatory nucleic acid adjuvant that selectively targets Toll-like receptor 3 (TLR3) in antigen-presenting dendritic cells (APCs) to safely induce antigen cross-presentation and subsequently induce an acquired immune response independent of inflammation. This review discusses the challenges faced in the clinical development of novel adjuvants. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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21 pages, 1145 KiB

Open AccessFeature PaperReview

RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

by Takuya Uehata and Osamu Takeuchi

Cells 2020, 9(7), 1701; https://doi.org/10.3390/cells9071701 - 16 Jul 2020

Cited by 34 | Viewed by 7170

Abstract

RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate [...] Read more.

RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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9 pages, 462 KiB

Open AccessFeature PaperReview

PD-1: Its Discovery, Involvement in Cancer Immunotherapy, and Beyond

by Yasumasa Ishida

Cells 2020, 9(6), 1376; https://doi.org/10.3390/cells9061376 - 01 Jun 2020

Cited by 29 | Viewed by 5301

Abstract

On December 10, 2018, I was sitting among the big crowd of audience, as one of the invited guests to the ceremony, in the Stockholm Concert Hall. When King of Sweden Carl XVI Gustaf bestowed the diploma and medal of Nobel Prize of [...] Read more.

On December 10, 2018, I was sitting among the big crowd of audience, as one of the invited guests to the ceremony, in the Stockholm Concert Hall. When King of Sweden Carl XVI Gustaf bestowed the diploma and medal of Nobel Prize of Physiology or Medicine 2018 on Dr. Tasuku Honjo and shook his hand for a while, surrounded by the thunderous applause and energetically blessing orchestral music, I thought that it had been a long journey for the molecule that we had first isolated in the early 1990s. Although it was truly a commemorable moment in the history of the programmed death-1 (PD-1) research, I believe we still have a long way to go. In this review article, I will explain why I think so, particularly by focusing on the potential role(s) that PD-1 appears to play in self-nonself discrimination by the immune system. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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23 pages, 1512 KiB

Open AccessReview

Dichotomous Regulation of Acquired Immunity by Innate Lymphoid Cells

by Takashi Ebihara

Cells 2020, 9(5), 1193; https://doi.org/10.3390/cells9051193 - 11 May 2020

Cited by 16 | Viewed by 4862

Abstract

The concept of innate lymphoid cells (ILCs) includes both conventional natural killer (NK) cells and helper ILCs, which resemble CD8⁺ killer T cells and CD4⁺ helper T cells in acquired immunity, respectively. Conventional NK cells are migratory cytotoxic cells that find [...] Read more.

The concept of innate lymphoid cells (ILCs) includes both conventional natural killer (NK) cells and helper ILCs, which resemble CD8⁺ killer T cells and CD4⁺ helper T cells in acquired immunity, respectively. Conventional NK cells are migratory cytotoxic cells that find tumor cells or cells infected with microbes. Helper ILCs are localized at peripheral tissue and are responsible for innate helper-cytokine production. Helper ILCs are classified into three subpopulations: T_H1-like ILC1s, T_H2-like ILC2s, and T_H17/T_H22-like ILC3s. Because of the functional similarities between ILCs and T cells, ILCs can serve as an innate component that augments each corresponding type of acquired immunity. However, the physiological functions of ILCs are more plastic and complicated than expected and are affected by environmental cues and types of inflammation. Here, we review recent advances in understanding the interaction between ILCs and acquired immunity, including T- and B-cell responses at various conditions. Immune suppressive activities by ILCs in particular are discussed in comparison to their immune stimulatory effects to gain precise knowledge of ILC biology and the physiological relevance of ILCs in human diseases. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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14 pages, 1532 KiB

Open AccessReview

Group 2 Innate Lymphoid Cells and the House Dust Mite-Induced Asthma Mouse Model

by Yuichiro Yasuda, Tatsuya Nagano, Kazuyuki Kobayashi and Yoshihiro Nishimura

Cells 2020, 9(5), 1178; https://doi.org/10.3390/cells9051178 - 09 May 2020

Cited by 28 | Viewed by 6491

Abstract

Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis of asthma. Recently, in addition to acquired immunity, innate immunity has also been thought to be involved [...] Read more.

Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis of asthma. Recently, in addition to acquired immunity, innate immunity has also been thought to be involved in asthma. Among innate immune cells, group 2 innate lymphoid cells (ILC2s) have been considered to be crucial for eosinophilic airway inflammation by releasing T helper 2 cytokines. Moreover, house dust mites (HDMs) belonging to group 1 act on airway epithelial cells not only as allergens but also as cysteine proteases. The production of interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP) from airway epithelial cells was induced by the protease activity of HDMs. These cytokines activate ILC2s, and activated ILC2s produce IL-5, IL-9, IL-13, and amphiregulin. Hence, the HDM-induced asthma mouse model greatly contributes to understanding asthma pathogenesis. In this review, we highlight the relationship between ILC2s and the HDM in the asthma mouse model to help researchers and clinicians not only choose a proper asthma mouse model but also to understand the molecular mechanisms underlying HDM-induced asthma. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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21 pages, 3733 KiB

Open AccessReview

Gut Microbiota, Its Role in Induction of Alzheimer’s Disease Pathology, and Possible Therapeutic Interventions: Special Focus on Anthocyanins

by Muhammad Sohail Khan, Muhammad Ikram, Jun Sung Park, Tae Ju Park and Myeong Ok Kim

Cells 2020, 9(4), 853; https://doi.org/10.3390/cells9040853 - 01 Apr 2020

Cited by 56 | Viewed by 6453

Abstract

The human gut is a safe environment for several microbes that are symbiotic and important for the wellbeing of human health. However, studies on gut microbiota in different animals have suggested that changes in the composition and structure of these microbes may promote [...] Read more.

The human gut is a safe environment for several microbes that are symbiotic and important for the wellbeing of human health. However, studies on gut microbiota in different animals have suggested that changes in the composition and structure of these microbes may promote gut inflammation by releasing inflammatory cytokines and lipopolysaccharides, gut-wall leakage, and may affect systemic inflammatory and immune mechanisms that are important for the normal functioning of the body. There are many factors that aid in the gut’s dysbiosis and neuroinflammation, including high stress levels, lack of sleep, fatty and processed foods, and the prolonged use of antibiotics. These neurotoxic mechanisms of dysbiosis may increase susceptibility to Alzheimer’s disease (AD) and other neurodegenerative conditions. Therefore, studies have recently been conducted to tackle AD-like conditions by specifically targeting gut microbes that need further elucidation. It was suggested that gut dyshomeostasis may be regulated by using available options, including the use of flavonoids such as anthocyanins, and restriction of the use of high-fatty-acid-containing food. In this review, we summarize the gut microbiota, factors promoting it, and possible therapeutic interventions especially focused on the therapeutic potential of natural dietary polyflavonoid anthocyanins. Our study strongly suggests that gut dysbiosis and systemic inflammation are critically involved in the development of neurodegenerative disorders, and the natural intake of these flavonoids may provide new therapeutic opportunities for preclinical or clinical studies. Full article

(This article belongs to the Special Issue Innate-Acquired Linkage in Immunotherapy)

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