Yumiko Tsukamoto's research while affiliated with The National Institute of Infectious Diseases and other places
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Publications (15)
Loss-of-function mutations in the lysosomal nucleoside transporter SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs. However, little is known about the mechanism by which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis in Slc29a3−/− mice was shown to depend on Toll-like...
SLC29A3, also known as ENT3, is a lysosomal transmembrane protein that transports nucleosides from the lysosomes to the cytoplasm ¹ . Loss-of-function mutations in SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs 2,3 . However, little is known about the mechanism through which lysosomal nucleos...
Mycobacterium bovis BCG has been the only practical vaccine for tuberculosis. However, BCG cannot fully prevent adult pulmonary tuberculosis. Therefore, the improvement of BCG vaccine is necessary. We previously produced recombinant (r) BCG (BCG-PEST) for the better control of tuberculosis. BCG-PEST was developed by introducing PEST-Heat Shock Prot...
Background and Aim
CpG motifs in DNA sequences are recognized by TLR9 and activate immune cells. Bacterial genomic DNA (gDNA) has modified cytosine bases (5-methylcytosine (5mC)) and modified adenine bases (6-methyladenine (6mA)). It is well-known that 5mC inhibits immune activation by CpG DNA; however, it is still unclear whether 6mA inhibits immu...
CpG motifs in DNA sequences are recognized by Toll-like receptor 9 and activate immune cells. Bacterial genomic DNA (gDNA) has modified cytosine bases (5-methylcytosine [5 mC]) and modified adenine bases (6-methyladenine [6 mA]). 5 mC inhibits immune activation by CpG DNA; however, it is unclear whether 6 mA inhibits immune activation by CpG DNA. M...
Enhancement of the T cell-stimulating ability of Mycobacterium bovis BCG (BCG) is necessary to develop an effective tuberculosis vaccine. For this purpose, we introduced the PEST-HSP70-major membrane protein-II (MMPII)-PEST fusion gene into ureC-gene depleted recombinant (r) BCG to produce BCG-PEST. The PEST sequence is involved in the proteasomal...
We have previously shown that the serodiagnosis using major membrane protein-II (MMP-II) is quite efficient in diagnosing leprosy. However, the detection rate of pauci-bacillary (PB) leprosy patients is still low. In this study, we examined the usefulness of major membrane protein-I (MMP-I) from M. leprae. The MMP-I-based serodiagnosis did not show...
Mycobacterium bovis bacillus Calmette-Guerin (BCG) is known to be only partially effective in inhibiting M. tuberculosis (MTB) multiplication in human. A new recombinant (r) urease-deficient BCG (BCG-dHCM) that secretes protein composed of heat shock protein (HSP)70, MTB-derived CysO and major membrane protein (MMP)-II was produced for the efficien...
For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein
composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted
the HSP70-MM...
Previously, we observed that both major membrane protein II of Mycobacterium leprae (MMP-ML) and its fusion with M. bovis BCG (BCG)-derived heat shock protein 70 (HSP70) (Fusion-ML) are immunogenic and that recombinant BCG secreting either of
these proteins effectively inhibits the multiplication of M. leprae in mice. Here, we purified M. tuberculo...
To activate naive T cells convincingly using Mycobacterium bovis bacillus Calmette-Guérin (BCG), recombinant BCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was...
Because Mycobacterium bovis bacillus Calmette-Guérin (BCG) unconvincingly activates human naive CD8(+) T cells, a rBCG (BCG-70M) that secretes a fusion protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed to poten...
IL-4 and 8-mercaptoguanosine (8-SGuo) stimulation of CD38-activated B cells induces μ to γ1 class switch recombination (CSR) at the DNA level leading to a high level of IgG1 production. Although some of signaling events initiated by IL-4 in activated B cells have been characterized, the involvement of TLR/MyD88 and Btk pathway in IL-4-dependent μ t...
Mature B cells expressing surface IgM as B cell receptor (BCR) consist of two B-cell subpopulations, B-1 and B-2 cells that regulate innate and acquired immunity, respectively. B-1 cells become natural Ig-producing plasma cells in response to natural ligands or self-antigens. Mature B-2 cells proliferate and differentiate into Ig-producing plasma c...
Mature B-2 cells expressing surface IgM and IgD proliferate upon stimulation by CD38, CD40 or lipopolysaccharide (LPS) and differentiate into IgG1-producing plasma cells in the presence of cytokines. The process of class switch recombination (CSR) from IgM to other isotypes is highly regulated by cytokines and activation-induced cytidine deaminase...
Citations
... After antigen and inflammatory stimulation, the expression of these molecules increases, activating T cells to initiate an adaptive immune response (Sabado et al., 2017). Toll-like receptors 9 (TLR9) are highly expressed in PDCs and activate the NF-kB pathway to produce type I IFN and other proinflammatory cytokines associated with antiviral immunity (Durai and Murphy, 2016;Tsukamoto et al., 2020). MyD88 is a prerequisite for IFN promoter activation. ...
... Numerous genes have been knocked out using this method in many Mycobacterium species, including M. bovis BCG substrains [36][37][38], virulent M. tb [39,40], and M. avium [41,42]. In 2014, an update of this method was published [43], to improve upon several rate-limiting steps of specialized transduction. ...
Reference: A guide to Mycobacterium mutagenesis
... In this study, secretion of IFN-γ, IL-5, and IL-10 cytokines was investigated as effector Th1 and Th2 cytokines (Takatsu et al. 2005;Castro et al. 2018) as well as the release of Granzyme B (an indicator of CTL activity) (Hagn and Jahrsdörfer 2012). Our data confirmed high levels of IFN-γ and also Granzyme B in groups immunized with homologous Nef-Vpr protein prime/protein boost regimen, and heterologous DNA + LL37 prime/protein boost regimen indicating direction of immune responses toward Th1 response and also CTL activity, respectively. ...
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... While these R123 neg CD23 -B cells are presumably mature naïve B cells, some appear to have downregulated their IgM and IgD B cell receptors and may correspond to a distinct mature B cell population with regulatory activity, mature IgD low/-B cells (BD L cells), that develops in parallel to FO B cells [42]. Other studies have shown that TLR7 and IL-4 stimulation induce isotype class switching in activated murine B cells [43]. Since CD23 is downregulated in isotype-switched B cells [43], the small subpopulation of sIgM -sIgDcells within the R123 neg CD23 -B cells alternatively may represent isotype switched B cells. ...
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![[object Object]](https://i1.rgstatic.net/ii/profile.image/393429436649472-1470812295068_Q64/Takuma-Shibata-2.jpg)
... Some other studies reveal that TLR2 engagement on CD4 + T cells may increase Mtb Ag-specific responses and contribute to protection against Mtb infection [63]. The role of such an engagement in the contribution of CD4 + cells against Mtb is supported by the study in which pretreatment with TLR2-antagonistic antibody significantly inhibits the cytokine production caused by a major membrane protein II of Mtb [64]. Furthermore, Mtb lipoproteins LprG and LpqH induce the activation of memory CD4+ T lymphocytes via the existence of TLR2 on their surface [65]. ...
... Supernatants of the cocultures were collected and analyzed for IL-6, IL-12p40, TNF-a, and IL-1b production by using an ELISA kit (R&D Systems), according to the protocol of the manufacturer. Ag presentation of rBCG-infected BMDCs to T cells was assessed using an autologous APC T cell coculture as previously described (29,30). Briefly, immature BMDCs were infected with either rBCG-pSO or rBCG-SOCS1DN at various MOIs and cultured for 24 h in the presence of rGM-CSF at 37˚C. ...
... Heat shock proteins are highly conserved cytoplasmic proteins during biological evolution. Recent studies have found that in addition to being an important molecular chaperone, GP96 can also transfer binding peptides to MHC-I molecules, thereby causing specific CTL responses [23][24][25]. A study found that compared with the polypeptide alone, HSP protein with mixed peptide and DC incubation produced stronger presentation [26]. ...
