Phosphatidic acid production on the vacuole harboring is a signal for recognition of interferon-induced GTPases.

The interferon (IFN)-inducible GTPases play a crucial role in cell autonomous immunity against intracellular pathogens. Particularly, these GTPases directly recognize the host membrane-derived vacuole containing pathogens and subsequently destroy it. Although it has been revealed that these GTPases target the membrane of ()-containing vacuole (LCV), molecular mechanism has been totally uncleared.

Discrepancies in the Diagnosis of Congenital Infection Between B1 Gene Semi-Nested Polymerase Chain Reaction and Serological Analyses.

Congenital () infection, which can be caused by a primary infection during pregnancy, results in severe neurological sequelae in affected children. We have been conducting a prospective cohort study since January 2019 on pregnant women who were suspected of having primary infection based on serological tests. In this study, congenital infection was diagnosed using semi-nested polymerase chain reaction (PCR) to detect the B1 gene in the body fluids of newborns.

Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology.

Alveolar macrophages (AMs) are essential for maintaining lung homeostasis. However, their roles in respiratory infections have been controversial because the methods of depleting them have often suffered from poor cell selectivity. To resolve this problem, we here used VeDTR technology to generate a transgenic mouse line in which AMs can be specifically depleted using diphtheria toxin.

IFN-γ-induced Th1-Treg polarization in inflamed brains limits exacerbation of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is the most widely used rodent model for multiple sclerosis. Interferon-γ (IFN-γ) and regulatory T cells (Tregs) are individually well known to play beneficial roles in amelioration of EAE. However, little is known about the relationship between IFN-γ and Tregs during the disease.

Toxoplasma GRA15 expression on dendritic cells inhibits B cell differentiation and antibody production.

One of the dense granule proteins named GRA15 in Toxoplasma gondii (T. gondii), is known to support an innate immune response in host through activation of NF-κB. However, little is known about advantages of GRA15 for parasites.

Tff1-expressing Tregs in lung prevent exacerbation of Bleomycin-induced pulmonary fibrosis.

Bleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis.

CRISPR screens identify genes essential for virulence among proteins of hyperLOPIT-unassigned subcellular localization in .

The research field to identify and characterize genes essential for virulence in has been dramatically advanced by a series of clustered regularly interspaced short palindromic repeats (CRISPR) screens. Although subcellular localizations of thousands of proteins were predicted by the spatial proteomic method called hyperLOPIT, those of more than 1,000 proteins remained unassigned, and their essentiality in virulence was also unknown. In this study, we generated two small-scale gRNA libraries targeting approximately 600 hyperLOPIT-unassigned proteins and performed CRISPR screens.

Individual Atg8 paralogs and a bacterial metabolite sequentially promote hierarchical CASM-xenophagy induction and transition.

Atg8 paralogs, consisting of LC3A/B/C and GBRP/GBRPL1/GATE16, function in canonical autophagy; however, their function is controversial because of functional redundancy. In innate immunity, xenophagy and non-canonical single membranous autophagy called "conjugation of Atg8s to single membranes" (CASM) eliminate bacteria in various cells. Previously, we reported that intracellular Streptococcus pneumoniae can induce unique hierarchical autophagy comprised of CASM induction, shedding, and subsequent xenophagy.

Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.

Irgb6 is a priming immune-related GTPase (IRG) that counteracts Toxoplasma gondii. It is known to be recruited to the low virulent type II T. gondii parasitophorous vacuole (PV), initiating cell-autonomous immunity.

Fusobacterium nucleatum infection activates the noncanonical inflammasome and exacerbates inflammatory response in DSS-induced colitis.

Caspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular contents. Fusobacterium nucleatum is a periodontal pathogen frequently detected in human cancer and inflammatory bowel diseases. Studies have reported that F.

A genetic method specifically delineates Th1-type Treg cells and their roles in tumor immunity.

Regulatory T (Treg) cells expressing the transcription factor (TF) Foxp3 also express other TFs shared by T helper (Th) subsets under certain conditions. Here, to determine the roles of T-bet-expressing Treg cells, we generate a mouse strain, called VeDTR, in which T-bet/Foxp3 double-positive cells are engineered to be specifically labeled and depleted by a combination of Cre- and Flp-recombinase-dependent gene expression control. Characterization of T-betFoxp3 cells using VeDTR mice reveals high resistance under oxidative stress, which is involved in accumulation of T-betFoxp3 cells in tumor tissues.

Host genetics highlights IFN-γ-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens.

Secreted virulence factors of Toxoplasma to survive in immune-competent hosts have been extensively explored by classical genetics and in vivo CRISPR screen methods, whereas their requirements in immune-deficient hosts are incompletely understood. Those of non-secreted virulence factors are further enigmatic. Here we develop an in vivo CRISPR screen system to enrich not only secreted but also non-secreted virulence factors in virulent Toxoplasma-infected C57BL/6 mice.

IWS1 Determines Fitness in Interferon-γ-Activated Host Cells and Mice by Indirectly Regulating ROP18 mRNA Expression.

Toxoplasma gondii secretes various virulence effector molecules into host cells to disrupt host interferon-γ (IFN-γ)-dependent immunity. Among these effectors, ROP18 directly phosphorylates and inactivates IFN-inducible GTPases, such as immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs), leading to the subversion of IFN-inducible GTPase-induced cell-autonomous immunity. The modes of action of ROP18 have been studied extensively; however, little is known about the molecular mechanisms by which ROP18 is produced in the parasite itself.

TFEB-mediated lysosomal exocytosis alleviates high-fat diet-induced lipotoxicity in the kidney.

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown.

Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine.

Immune response induced in rodents by anti-CoVid19 plasmid DNA vaccine via pyro-drive jet injector inoculation.

There is an urgent need to stop the coronavirus disease 2019 (COVID-19) pandemic through the development of efficient and safe vaccination methods. Over the short term, plasmid DNA vaccines can be developed as they are molecularly stable, thus facilitating easy transport and storage. pVAX1-SARS-CoV2-co was designed for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) S protein.

Anti-Toxoplasma host defense systems and the parasitic counterdefense mechanisms.

Toxoplasma gondii is an intracellular parasite that does not differentiate among hosts and is capable of infecting nearly all warm-blooded vertebrates. Although about 30% of the human population is thought to be infected with T. gondii, it is one of the most common opportunistic infections that does not cause serious symptoms when the immune system is functioning normally.

A prospective cohort study of newborns born to mothers with serum Toxoplasma gondii immunoglobulin M positivity during pregnancy.

Introduction: The aims were to investigate the clinical characteristics of Toxoplasma gondii (T. gondii) immunoglobulin (Ig) M-positive mothers and to clarify the incidences of serum T. gondii IgM or blood T.

Structural basis of membrane recognition of vacuole by Irgb6.

The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6.