Shizuo Akira

Bio: Shizuo Akira is an academic researcher from Osaka University. The author has contributed to research in topics: Innate immune system & Immune system. The author has an hindex of 261, co-authored 1308 publications receiving 320561 citations. Previous affiliations of Shizuo Akira include University of California, Berkeley & Wakayama Medical University.

Plasmodium products persist in the bone marrow and promote chronic bone loss.

Abstract: Although malaria is a life-threatening disease with severe complications, most people develop partial immunity and suffer from mild symptoms However, incomplete recovery from infection causes chronic illness, and little is known of the potential outcomes of this chronicity We found that malaria causes bone loss and growth retardation as a result of chronic bone inflammation induced by Plasmodium products Acute malaria infection severely suppresses bone homeostasis, but sustained accumulation of Plasmodium products in the bone marrow niche induces MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression and overstimulation of osteoclastogenesis, favoring bone resorption Infection with a mutant parasite with impaired hemoglobin digestion that produces little hemozoin, a major Plasmodium by-product, did not cause bone loss Supplementation of alfacalcidol, a vitamin D3 analog, could prevent the bone loss These results highlight the risk of bone loss in malaria-infected patients and the potential benefits of coupling bone therapy with antimalarial treatment

Oncolytic Reovirus Inhibits Immunosuppressive Activity of Myeloid-Derived Suppressor Cells in a TLR3-Dependent Manner.

Abstract: Oncolytic reovirus, which possesses 10 segments of dsRNA genome, mediates antitumor effects via not only virus replication in a tumor cell-specific manner, but also activation of antitumor immunity; however, the mechanism(s) of reovirus-induced activation of antitumor immunity have not been fully elucidated. Recent studies have demonstrated that overcoming an immunosuppressive environment in tumor-bearing hosts is important to achieve efficient activation of antitumor immunity. Among the various types of cells involved in immunosuppression, it has been revealed that myeloid-derived suppressor cells (MDSCs) are significantly increased in tumor-bearing hosts and play crucial roles in the immunosuppression in tumor-bearing hosts. In this study, we examined whether reovirus inhibits the immunosuppressive activity of MDSCs, resulting in efficient activation of immune cells after in vivo administration. The results showed that splenic MDSCs recovered from PBS-treated tumor-bearing mice significantly suppressed the Ag-specific proliferation of CD8+ T cells. In contrast, the suppressive activity of MDSCs on T cell proliferation was significantly reduced after reovirus administration. Reovirus also inhibited the immunosuppressive activity of MDSCs in IFN-β promoter stimulator-1 knockout (KO) mice and in wild-type mice. In contrast, the immunosuppressive activity of MDSCs in TLR-3 KO mice was not significantly altered by reovirus treatment. The activation levels of CD4+ and CD8+ T cells were significantly lower in TLR3 KO mice than in wild-type mice after reovirus administration. These results indicate that reovirus inhibits the immunosuppressive activity of MDSCs in a TLR3, but not IFN-β promoter stimulator-1, signaling-dependent manner.

MyD88 protects from lethal encephalitis during infection with vesicular stomatitis virus.

Abstract: MyD88 is a key adaptor molecule in innate resistance, engaged in most Toll-like receptor, as well as IL-1 and IL-18, signalling. Here, we analyzed the role of MyD88 in innate resistance during infection with vesicular stomatitis virus (VSV) using myd88(-/-) mice. We found an increased susceptibility to VSV in myd88(-/-) mice, which was not explained by reduced type I IFN or neutralizing antibody responses. Susceptibility of myd88(-/-) mice correlated with impaired recruitment of immune cells to the site of infection. In the absence of MyD88 signalling, VSV rapidly spread to the spinal cord and brain causing lethal encephalitis.

Toll-Like Receptor Signaling: Emerging Opportunities in Human Diseases and Medicine

Abstract: The family of Toll-like receptors (TLR1-TLR11) provides host defense in mammals by inducing pro- inflammatory innate immune response upon recognition of conserved structural component in pathogens. TLR mediated activation of signaling pathways that induce the expression of proinflammato ry molecules is one of the well-studied but ever expanding fields of immunology. As a result, a wealth of information has been obtained which includes the identification of specific ligands of individual TLR, elucidation of their downstream signaling pathways, function of different adaptor proteins, activation of protein kinases and transcription factors that transcribe the genes for inflammatory molecules. TLRs not only sense microbial invasion but also can be activated by endogenous molecules as well as low molecular weight synthetic compounds. Given the role of innate immune machinery to provoke inflammation in host, TLRs signaling may be involved in many acute and chronic inflammatory processes in sterile and post-infection conditions such as, atherosclerosis, leprosy, inflammatory bowel syndrome (IBD), lung airway hyperactivity in allergic asthma, and in sepsis. By the same token, TLRs can also be associated with autoimmune diseases such as systemic lupus erythematosus (SLE) or other immune unresponsive diseases like cancer. In addition, synthetic organic compounds which enhance the function of TLRs can also be useful as potential adjutants to improve conventional vaccination strategy. Here we summarize the recent development on possible modulation of the TLR signaling pathway for therapeutic solution of multiple immune-related diseases.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.

Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

Cancer-related inflammation.

Abstract: The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.