Toshi Nagata - Academia.edu (original) (raw)
Papers by Toshi Nagata
Immunology, Jan 16, 2016
Bone-marrow-derived macrophages are divided into two phenotypically and functionally distinct sub... more Bone-marrow-derived macrophages are divided into two phenotypically and functionally distinct subsets, M1 and M2 macrophages. Recently, it was shown that adoptive transfer of M2-polarized peritoneal macrophages reduced the severity of experimental colitis in mice. However, it is still unclear whether peritoneal macrophages possess the same ability to be polarized to cells with functionally different phenotypes and cytokine production patterns as bone-marrow-derived macrophages. To address this question, we examined the ability of peritoneal macrophages to be polarized to the M1 and M2 phenotypes and determined the specific cytokine profiles of cells with each phenotype. We showed that peritoneal macrophages, as well as bone-marrow-derived macrophages, were differentiated into M1 and M2 phenotypes following stimulation with interferon-γ (IFN-γ) and interleukin-4 (IL-4)/IL-13, respectively. Following in vitro stimulation with lipopolysaccharide, M2-polarized peritoneal macrophages pre...
FEMS Immunology & Medical Microbiology, 2011
Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chap... more Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chaperones called stress proteins that can activate innate and adaptive immune responses. We evaluated the effect of a fusion DNA vaccine that encoded mycobacterial HSP70 and MPT51, a major secreted protein of Mycobacterium tuberculosis. Spleen cells from mice immunized with fusion DNA of full-length HSP70 and MPT51 produced a higher amount of interferon-g (IFN-g) in response to the CD41, but not the CD81 T-cell epitope peptide on MPT51 than those from mice immunized with MPT51 DNA. Furthermore, because HSP70 comprises the N-terminal ATPase domain and the C-terminal peptide-binding domain, we attempted to identify the domain responsible for its enhancing effect. The fusion DNA vaccine that encoded the C-terminal domain of HSP70 and MPT51 induced a higher MPT51-specific IFN-g production by CD41 T cells than the vaccine that encoded MPT51 alone, whereas that with the N-terminal domain did not. Similar results were obtained by immunization with the fusion proteins. These results suggest that the DNA vaccine that encodes a chimeric antigen molecule fused with mycobacterial HSP70, especially with its C-terminal domain, can induce a stronger antigen-specific T-helper cell type 1 response than antigen DNA alone.
BioScience Trends
Japan has been categorized as a super-aged society. The percentage of the population over 65 year... more Japan has been categorized as a super-aged society. The percentage of the population over 65 years of age in Japan is predicted to be 40.5% by 2055 (1). A community-based integrated care system is defined as a system that includes not only medical and nursing care but also welfare services in order to guarantee safety, security and health according to needs in a local area (2,3). It is indispensable to create the system as a mechanism to provide these services comprehensively and continuously in local communities. The system is based on four different care concepts: governmental care (Ko-jo), social solidarity care (Kyo-jo), self-help (Jijo), and mutual aid (Go-jo) (4). Mutual aid (Go-jo) is the voluntary mutual support of local people. As it is difficult to expect to greatly expand social solidarity care, great expectation is given to mutual aid conducted by local residents and others (5). We examined the actual status of Japanese high school students' perception of mutual aid and the related factors. The reason that we focused on high school students is that they constitute an essential generation that will be responsible for a communitybased integrated care system in the future.
American journal of infection control, Jan 27, 2015
Central line-associated bloodstream infection (CLABSI) is an important concern associated with ce... more Central line-associated bloodstream infection (CLABSI) is an important concern associated with central venous catheter (CVC) use. The objective of this study was to determine the influences of CVC access sites, CVC types, and presumed causative microorganisms on CLABSI occurrence in an acute care hospital. We conducted a prospective, observational study of CLABSI occurrence for 3 consecutive years in a 600-bed Japanese acute care hospital. Data collected included patient characteristics, CVC access sites, CVC types, and microorganisms isolated by blood culture. For 1,650 CVCs used for 1,237 patients, 39 cases of infection were identified. Most infections had occurred within 1 month of CVC insertion. Maximal sterile barrier precautions had been used for most cases (97.3%). The average CLABSI occurrence days with internal jugular vein access were shorter than those with subclavian vein access and femoral vein access. CLABSI rates were 1.1 and 0.7 for single- and multilumen CVCs, respe...
![Research paper thumbnail of [T-cell-oriented vaccination against Mycobacterium tuberculosis]](https://attachments.academia-assets.com/77300240/thumbnails/1.jpg)
](Nihon saikingaku zasshi. Japanese journal of bacteriology, 2010
Journal of Natural Medicines, 2007
ABSTRACT Effects of Hochu-ekki-to (TJ-41) on the course of lethal rodent malarial infection with ... more ABSTRACT Effects of Hochu-ekki-to (TJ-41) on the course of lethal rodent malarial infection with Plasmodium chabaudi AS were examined in male A/J mice. We examined the mortality, parasitemia and serum cytokines such as IL-12, IFN-γ and IL-4 in the infected and TJ-41-treated/infected mice. There was a significant difference in mortality between infected and treated/infected mice. A high mortality was observed in male mice after infection with P. chabaudi AS. In mice treated with TJ-41, control of the primary infection was achieved, and significantly lower mortality was observed. All surviving males in the treated/infected group showed somewhat smaller peak parasitemias than those in infected controls. Mice in the infected and treated/infected groups displayed significantly elevated serum IL-12 levels on day 4 of infection when compared with the levels from the uninfected animals. Mice in the infected and treated/infected groups displayed significantly elevated serum IFN-γ levels when compared with the levels from the uninfected animals. Furthermore, a significantly higher IFN-γ level was seen in the treated/infected group than that in the infected group on day 4 of infection. The present results suggest that an early production of IFN-γ in the TJ-41-treated/infected mice is associated with a decrease of parasitemia, being responsible for the survival of mice.
Vaccine, 2000
Utilizing a plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope and that encoding ... more Utilizing a plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope and that encoding ovalbumin (OVA), we compared the reproducibility in the induction of immune responses by gene gun and intramuscular immunization. As compared to intramuscular inoculation, gene gun DNA immunization appeared to bring about highly reproducible and reliable results in the induction of speci®c CTL and IFN-g production to the CTL epitope and production of anti-OVA IgG. The results obtained by intramuscular inoculation vary signi®cantly. Our data shown here strongly suggest that gene gun immunization of skin is a much more reliable method for DNA vaccination to induce eective immune responses in an animal model.
The International Journal of Tuberculosis and Lung Disease, 2013
DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their pr... more DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their products are demonstrated to have immunogenicity in M. tuberculosis-infected individuals, suggesting that DosR regulon-encoded proteins are suitable targets for vaccines to control the reactivation of dormant M. tuberculosis. Prospective analysis of T-cell and antibody responses against DosR regulon-encoded antigens in M. tuberculosis-infected individuals in Japan to identify effective vaccine targets. T-cell responses against 33 DosR regulon-encoded antigens were investigated in 26 consecutive M. tuberculosis-infected individuals--14 with latent tuberculosis infection (LTBI) and 12 with active pulmonary tuberculosis (PTB)--using enzyme-linked immunosorbent spot assay, and antibody responses in 42 consecutive individuals, 14 with LTBI and 28 with PTB. Six antigens (Rv0570, Rv1996, Rv2004c, Rv2028c, Rv2029c and Rv3133c) induced stronger T-cell responses in LTBI than in PTB, In contrast, antigen-specific antibody responses to five antigens (Rv0080, Rv1738, Rv2007c, Rv2031c and Rv2032) were found to be stronger in PTB than in LTBI cases. T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.
International Journal of Infectious Diseases, 2008
Introduction: Though PE and PPE families have been thought to play important roles in mycobacteri... more Introduction: Though PE and PPE families have been thought to play important roles in mycobacterial pathogenesis from an antigenic as well as immunological view point, there has not been much information available regarding their physiological relevance, more so in the light of the fact that mycobacteria have been highly successful in devising strategies of immune evasion. One of the PPE proteins, Rv1196 (PPE18 or mtb39a) was found to be expressed during infection and present exclusively in M. tuberculosis and M. bovis BCG but not in other mycobacterial species. Further, the microarray studies indicate that Rv1196 is one of the proteins involved in maintaining long term survival of M. tuberculosis within the host. Since Th2 plays an important role in activating M. tuberculosis pathogenesis, we have evaluated the role of Rv1196 protein to interact with macrophage and affect the Th2 balance. Method: Cytokine induction was measured by enzyme immunoassay (EIA). Interacting receptor on macrophages were identified by flow cytometry and coimmunoprecipitation assay using specific antibody. The p38 MAPK and ERK 1/2 and JNK signaling was examined by Western blotting and flow cytometry Results: We demonstrate that the PPE protein, Rv1196 stimulates macrophages to secrete interleukin (IL)-10 cytokine, which favors a Th2 T-cell response congenial for mycobacterial survival. However, it does not significantly affect the production of inflammatory cytokines like IL-12, TNF-␣ as well as nitric oxide production. IL-10 induction was found to be dependent on specific interaction of Rv1196 protein to the toll-like receptor (TLR) 2 on membrane. We found that an early and sustained activation of p38 MAPK (but not ERK 1/2 and JNK) downstream of TLR2 was critical for triggering of IL-10 by Rv1196. Conclusion: Our data suggest a unique role of the M. tuberculosis PPE protein in eliciting an anti-Th1 response critical for survival of the bacteria.
Procedia in Vaccinology, 2010
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), persists within infec... more Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), persists within infected macrophages for long periods of time in a metabolically inactive but reversible state known as dormancy. Since the majority of adult pulmonary TB is caused by the reactivation of persistent Mtb, novel vaccines to protect against disease reactivation and novel biomarkers to provide the basis of new diagnosis
Immunology, Jan 16, 2016
Bone-marrow-derived macrophages are divided into two phenotypically and functionally distinct sub... more Bone-marrow-derived macrophages are divided into two phenotypically and functionally distinct subsets, M1 and M2 macrophages. Recently, it was shown that adoptive transfer of M2-polarized peritoneal macrophages reduced the severity of experimental colitis in mice. However, it is still unclear whether peritoneal macrophages possess the same ability to be polarized to cells with functionally different phenotypes and cytokine production patterns as bone-marrow-derived macrophages. To address this question, we examined the ability of peritoneal macrophages to be polarized to the M1 and M2 phenotypes and determined the specific cytokine profiles of cells with each phenotype. We showed that peritoneal macrophages, as well as bone-marrow-derived macrophages, were differentiated into M1 and M2 phenotypes following stimulation with interferon-γ (IFN-γ) and interleukin-4 (IL-4)/IL-13, respectively. Following in vitro stimulation with lipopolysaccharide, M2-polarized peritoneal macrophages pre...
FEMS Immunology & Medical Microbiology, 2011
Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chap... more Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chaperones called stress proteins that can activate innate and adaptive immune responses. We evaluated the effect of a fusion DNA vaccine that encoded mycobacterial HSP70 and MPT51, a major secreted protein of Mycobacterium tuberculosis. Spleen cells from mice immunized with fusion DNA of full-length HSP70 and MPT51 produced a higher amount of interferon-g (IFN-g) in response to the CD41, but not the CD81 T-cell epitope peptide on MPT51 than those from mice immunized with MPT51 DNA. Furthermore, because HSP70 comprises the N-terminal ATPase domain and the C-terminal peptide-binding domain, we attempted to identify the domain responsible for its enhancing effect. The fusion DNA vaccine that encoded the C-terminal domain of HSP70 and MPT51 induced a higher MPT51-specific IFN-g production by CD41 T cells than the vaccine that encoded MPT51 alone, whereas that with the N-terminal domain did not. Similar results were obtained by immunization with the fusion proteins. These results suggest that the DNA vaccine that encodes a chimeric antigen molecule fused with mycobacterial HSP70, especially with its C-terminal domain, can induce a stronger antigen-specific T-helper cell type 1 response than antigen DNA alone.
BioScience Trends
Japan has been categorized as a super-aged society. The percentage of the population over 65 year... more Japan has been categorized as a super-aged society. The percentage of the population over 65 years of age in Japan is predicted to be 40.5% by 2055 (1). A community-based integrated care system is defined as a system that includes not only medical and nursing care but also welfare services in order to guarantee safety, security and health according to needs in a local area (2,3). It is indispensable to create the system as a mechanism to provide these services comprehensively and continuously in local communities. The system is based on four different care concepts: governmental care (Ko-jo), social solidarity care (Kyo-jo), self-help (Jijo), and mutual aid (Go-jo) (4). Mutual aid (Go-jo) is the voluntary mutual support of local people. As it is difficult to expect to greatly expand social solidarity care, great expectation is given to mutual aid conducted by local residents and others (5). We examined the actual status of Japanese high school students' perception of mutual aid and the related factors. The reason that we focused on high school students is that they constitute an essential generation that will be responsible for a communitybased integrated care system in the future.
American journal of infection control, Jan 27, 2015
Central line-associated bloodstream infection (CLABSI) is an important concern associated with ce... more Central line-associated bloodstream infection (CLABSI) is an important concern associated with central venous catheter (CVC) use. The objective of this study was to determine the influences of CVC access sites, CVC types, and presumed causative microorganisms on CLABSI occurrence in an acute care hospital. We conducted a prospective, observational study of CLABSI occurrence for 3 consecutive years in a 600-bed Japanese acute care hospital. Data collected included patient characteristics, CVC access sites, CVC types, and microorganisms isolated by blood culture. For 1,650 CVCs used for 1,237 patients, 39 cases of infection were identified. Most infections had occurred within 1 month of CVC insertion. Maximal sterile barrier precautions had been used for most cases (97.3%). The average CLABSI occurrence days with internal jugular vein access were shorter than those with subclavian vein access and femoral vein access. CLABSI rates were 1.1 and 0.7 for single- and multilumen CVCs, respe...
Nihon saikingaku zasshi. Japanese journal of bacteriology, 2010
Journal of Natural Medicines, 2007
ABSTRACT Effects of Hochu-ekki-to (TJ-41) on the course of lethal rodent malarial infection with ... more ABSTRACT Effects of Hochu-ekki-to (TJ-41) on the course of lethal rodent malarial infection with Plasmodium chabaudi AS were examined in male A/J mice. We examined the mortality, parasitemia and serum cytokines such as IL-12, IFN-γ and IL-4 in the infected and TJ-41-treated/infected mice. There was a significant difference in mortality between infected and treated/infected mice. A high mortality was observed in male mice after infection with P. chabaudi AS. In mice treated with TJ-41, control of the primary infection was achieved, and significantly lower mortality was observed. All surviving males in the treated/infected group showed somewhat smaller peak parasitemias than those in infected controls. Mice in the infected and treated/infected groups displayed significantly elevated serum IL-12 levels on day 4 of infection when compared with the levels from the uninfected animals. Mice in the infected and treated/infected groups displayed significantly elevated serum IFN-γ levels when compared with the levels from the uninfected animals. Furthermore, a significantly higher IFN-γ level was seen in the treated/infected group than that in the infected group on day 4 of infection. The present results suggest that an early production of IFN-γ in the TJ-41-treated/infected mice is associated with a decrease of parasitemia, being responsible for the survival of mice.
Vaccine, 2000
Utilizing a plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope and that encoding ... more Utilizing a plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope and that encoding ovalbumin (OVA), we compared the reproducibility in the induction of immune responses by gene gun and intramuscular immunization. As compared to intramuscular inoculation, gene gun DNA immunization appeared to bring about highly reproducible and reliable results in the induction of speci®c CTL and IFN-g production to the CTL epitope and production of anti-OVA IgG. The results obtained by intramuscular inoculation vary signi®cantly. Our data shown here strongly suggest that gene gun immunization of skin is a much more reliable method for DNA vaccination to induce eective immune responses in an animal model.
The International Journal of Tuberculosis and Lung Disease, 2013
DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their pr... more DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their products are demonstrated to have immunogenicity in M. tuberculosis-infected individuals, suggesting that DosR regulon-encoded proteins are suitable targets for vaccines to control the reactivation of dormant M. tuberculosis. Prospective analysis of T-cell and antibody responses against DosR regulon-encoded antigens in M. tuberculosis-infected individuals in Japan to identify effective vaccine targets. T-cell responses against 33 DosR regulon-encoded antigens were investigated in 26 consecutive M. tuberculosis-infected individuals--14 with latent tuberculosis infection (LTBI) and 12 with active pulmonary tuberculosis (PTB)--using enzyme-linked immunosorbent spot assay, and antibody responses in 42 consecutive individuals, 14 with LTBI and 28 with PTB. Six antigens (Rv0570, Rv1996, Rv2004c, Rv2028c, Rv2029c and Rv3133c) induced stronger T-cell responses in LTBI than in PTB, In contrast, antigen-specific antibody responses to five antigens (Rv0080, Rv1738, Rv2007c, Rv2031c and Rv2032) were found to be stronger in PTB than in LTBI cases. T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.
International Journal of Infectious Diseases, 2008
Introduction: Though PE and PPE families have been thought to play important roles in mycobacteri... more Introduction: Though PE and PPE families have been thought to play important roles in mycobacterial pathogenesis from an antigenic as well as immunological view point, there has not been much information available regarding their physiological relevance, more so in the light of the fact that mycobacteria have been highly successful in devising strategies of immune evasion. One of the PPE proteins, Rv1196 (PPE18 or mtb39a) was found to be expressed during infection and present exclusively in M. tuberculosis and M. bovis BCG but not in other mycobacterial species. Further, the microarray studies indicate that Rv1196 is one of the proteins involved in maintaining long term survival of M. tuberculosis within the host. Since Th2 plays an important role in activating M. tuberculosis pathogenesis, we have evaluated the role of Rv1196 protein to interact with macrophage and affect the Th2 balance. Method: Cytokine induction was measured by enzyme immunoassay (EIA). Interacting receptor on macrophages were identified by flow cytometry and coimmunoprecipitation assay using specific antibody. The p38 MAPK and ERK 1/2 and JNK signaling was examined by Western blotting and flow cytometry Results: We demonstrate that the PPE protein, Rv1196 stimulates macrophages to secrete interleukin (IL)-10 cytokine, which favors a Th2 T-cell response congenial for mycobacterial survival. However, it does not significantly affect the production of inflammatory cytokines like IL-12, TNF-␣ as well as nitric oxide production. IL-10 induction was found to be dependent on specific interaction of Rv1196 protein to the toll-like receptor (TLR) 2 on membrane. We found that an early and sustained activation of p38 MAPK (but not ERK 1/2 and JNK) downstream of TLR2 was critical for triggering of IL-10 by Rv1196. Conclusion: Our data suggest a unique role of the M. tuberculosis PPE protein in eliciting an anti-Th1 response critical for survival of the bacteria.
Procedia in Vaccinology, 2010
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), persists within infec... more Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), persists within infected macrophages for long periods of time in a metabolically inactive but reversible state known as dormancy. Since the majority of adult pulmonary TB is caused by the reactivation of persistent Mtb, novel vaccines to protect against disease reactivation and novel biomarkers to provide the basis of new diagnosis