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.

A Role of Toll-IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β in the Host Response to Pseudomonas aeruginosa Lung Infection in Mice

Abstract: Toll-IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) is an adaptor molecule that mediates a distinct TLR signaling pathway. Roles of TRIF in the host defense have been primarily associated with virus infections owing to the induction of IFN-alphabeta. In this study, we investigated a role of TRIF in Pseudomonas aeruginosa infection. In vitro, TRIF-deficient mouse alveolar and peritoneal macrophages showed a complete inhibition of RANTES (CCL5) production, severely impaired TNF and KC (CXCL1) production, and reduced NF-kappaB activation in response to P. aeruginosa stimulation. In vivo, TRIF-deficient mice showed a complete inhibition of RANTES production, a severely impaired TNF and KC production, and an efficient MIP-2 and IL-1beta production in the lung following P. aeruginosa infection. This outcome was associated with a delayed recruitment of neutrophils into the airways. These results suggest that TRIF mediates a distinct cytokine/chemokine profile in response to P. aeruginosa infection. P. aeruginosa-induced RANTES production is completely dependent on TRIF pathway in mice. Importantly, TRIF deficiency leads to impaired clearance of P. aeruginosa from the lung during the initial 24-48 h of infection. Thus, TRIF represents a novel mechanism involved in the development of host response to P. aeruginosa infection.

'Toll' gates for future immunotherapy.

Abstract: Toll-like receptors (TLRs) are evolutionary conserved transmembrane proteins that recognize a unique pattern of molecules derived from pathogens or damaged cells, triggering robust but defined innate immune responses. TLR-mediated innate and/or adaptive immune responses play an important role in a variety of diseases including infectious diseases, sepsis, autoimmune diseases, allergy, and atherosclerosis. Each TLR displays a differential expression pattern, intracellular localization and signaling pathway, resulting in distinct immune responses. A variety of new TLR ligands including agonists (e.g. urinary Tamm-Horsfall glycoprotein as a TLR4 ligand, siRNA as TLR3 or 7 ligand, Plasmodium falciparum Hemozoin as a TLR9 ligand, Profilin-like protein in Toxoplasma gondii as a TLR11 ligand) and antagonists (G-rich oligodeoxynucleotides as antagonist for TLR9) have been identified, and some of other TLR ligands are already under clinical trials. The manipulation or intervention of TLR-mediated immune responses is a possible multiple 'Toll' gate for future developments of immunotherapies.

Acute inhibition of TAK1 protects against neuronal death in cerebral ischemia.

Abstract: Neuronal apoptosis contributes to ischemic brain damage and neurodegenerative disorders. Key regulators of neuronal apoptosis are the transcription factor NF-κB and the MAP kinases p38/MAPK and JNK, which share a common upstream activator, the mitogen-activated protein kinase kinase kinase (MAP3K) TGFβ-activated kinase 1 (TAK1). Here we investigate the function of TAK1 in ischemia-induced neuronal apoptosis. In primary cortical neurons, TAK1 was activated by oxygen glucose deprivation (OGD), an in vitro model of cerebral ischemia. We found that short-term inhibition of TAK1 protected against OGD in vitro and reduced the infarct volume after middle cerebral artery occlusion in vivo. Prolonged inhibition or deletion of the TAK1 gene in neurons was, however, not protective. Short-term, but not prolonged inhibition of TAK1 interfered with the activation of p38/MAPK and JNK by OGD, the induction of the pro-oxidative genes Cox-2, Nox-2, and p40phox, and the formation of superoxide. We found that prolonged TAK1 inhibition upregulated another MAP3K, apoptosis signal-regulating kinase-1, which is able to compensate for TAK1 inhibition. Our study demonstrates that TAK1 is a central target for short-term inhibition of key signaling pathways and neuroprotection in cerebral ischemia.

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.