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777 results on '"Fujino, Masayuki"'

9. Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets

Author

Fujino, Masayuki, Sato, Hirotaka, Okamura, Tomotaka, Uda, Akihiko, Takeda, Satoshi, Ahmed, Nursarat, Shichino, Shigeyuki, Shiino, Teiichiro, Saito, Yohei, Watanabe, Satoru, Sugimoto, Chie, Kuroda, Marcelo J, Ato, Manabu, Nagai, Yoshiyuki, Izumo, Shuji, Matsushima, Kouji, Miyazawa, Masaaki, Ansari, Aftab A, Villinger, Francois, and Mori, Kazuyasu

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Sexually Transmitted Infections, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Inflammatory and immune system, Infection, Good Health and Well Being, Animals, CD4-Positive T-Lymphocytes, Chemokine CXCL10, Gene Expression, Gene Expression Profiling, Immunity, Innate, Macaca mulatta, Macrophages, Male, Monocytes, Receptors, CXCR3, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, T-Lymphocyte Subsets, Simian immunodeficiency virus, CD4+ T cell, CXCL10, CXCR3, SIV, Th1, glycosylation, innate immunity, macrophages, monocytes, pathogenesis, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4+ T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4+ T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3+ CCR5+ CD4+ T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3+ T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14+ CD16+ monocytes and MAC387+ macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387+ macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages.IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4+ T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3+ CCR5+ CD4+ T (Th1) cells during the primary infection, thereby compromising the cellular immune response. Thus, we hypothesized that distinct host responses are elicited by the infections with two different viruses. We found that SIVmac239 induced distinctly higher levels of inflammatory Th1 responses than Δ5G. In particular, SIVmac239 infection elicited robust expression of CXCL10, a chemokine for CXCR3+ cells, in CD14+ CD16+ monocytes and MAC387+ macrophages recently infiltrated in SLOs. In contrast, Δ5G infection elicited only modest inflammatory responses. These results suggest that the glycosylation of Env modulates the inflammatory/Th1 responses through the monocyte/macrophage subsets and elicits marked differences in SIV infection and clinical outcomes.

Published
2017

30. Low-molecular-weight anti-HIV-1 agents targeting HIV-1 capsid proteins

Author

Kobayakawa, Takuya, primary, Yokoyama, Masaru, additional, Tsuji, Kohei, additional, Fujino, Masayuki, additional, Kurakami, Masaki, additional, Onishi, Takato, additional, Boku, Sayaka, additional, Ishii, Takahiro, additional, Miura, Yutaro, additional, Shinohara, Kouki, additional, Kishihara, Yuki, additional, Ohashi, Nami, additional, Kotani, Osamu, additional, Murakami, Tsutomu, additional, Sato, Hironori, additional, and Tamamura, Hirokazu, additional

Published
2023
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43. Dexmedetomidine versus fentanyl for sedation in extremely preterm infants.

Author

Nakauchi, Chiharuko, Miyata, Masafumi, Kamino, Shigemitsu, Funato, Yusuke, Manabe, Masahiko, Kojima, Arisa, Kawai, Yuri, Uchida, Hidetoshi, Fujino, Masayuki, and Boda, Hiroko

Subjects
DRUG efficacy, INFANT development, PHENYLPROPANOLAMINE, FENTANYL, RETROSPECTIVE studies, GESTATIONAL age, TREATMENT effectiveness, COMPARATIVE studies, HOSPITAL mortality, PRE-tests & post-tests, DESCRIPTIVE statistics, DRUG side effects
Abstract

Background: Few studies have compared the efficacy and complications of dexmedetomidine (DEX) and fentanyl (FEN) in extremely preterm infants. Methods: We conducted a single‐institution, retrospective controlled before and after study of preterm infants before 28 weeks of gestation admitted between April 2010 and December 2018 to compare the complications and efficacy of DEX and FEN for preterm infants. Patients were administered FEN prior to 2015 and DEX after 2015 as the first‐line sedative. A composite outcome of death during hospitalization and developmental quotient (DQ) < 70 at a corrected age of 3 years was compared as the primary outcome. Secondary outcomes including postmenstrual weeks at extubation, days of age when full enteral feeding was achieved and additional sedation by phenobarbital (PB) were compared. Results: Sixty‐six infants were enrolled into the study. The only perinatal factor that differed between the FEN (n = 33) and DEX (n = 33) groups was weeks of gestation. The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different. Postmenstrual weeks at extubation did not significantly differ between groups after adjustment for weeks of gestation and being small for gestational age. On the other hand, full feeding was significantly prolonged by DEX (p = 0.031). Additional sedation was less common in the DEX group (p = 0.044). Conclusion: The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different by DEX or FEN for primary sedation. Prospective randomized controlled trials should examine the long‐term effects on development. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Standardized endoscopic reporting

Author

Aabakken, Lars, Barkun, Alan N, Cotton, Peter B, Fedorov, Evgeny, Fujino, Masayuki A, Ivanova, Ekaterina, Kudo, Shin-ei, Kuznetzov, Konstantin, de Lange, Thomas, Matsuda, Koji, Moine, Olivier, Rembacken, Björn, Rey, Jean-Francois, Romagnuolo, Joseph, Rösch, Thomas, Sawhney, Mandeep, Yao, Kenshi, and Waye, Jerome D

Published
2014
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50. Protective immune responses elicited by deglycosylated live-attenuated SIV vaccine are associated with IL-15 effector functions

Author

Watanabe, Satoru, Fujino, Masayuki, Saito, Yohei, Ahmed, Nursarat, Sato, Hirotaka, Sugimoto, Chie, Okamura, Tomotaka, Hanaki, Kenichi, Nakayama, Emi E., Shioda, Tatsuo, Matsushima, Kouji, Ansari, Aftab A., Villinger, Francois, and Mori, Kazuyasu

Subjects
Interleukin-15, Male, Vaccination, SAIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, CD8-Positive T-Lymphocytes, Viral Load, Antibodies, Viral, Vaccines, Attenuated, Virus Replication, Macaca mulatta, Article, Immunity, Innate, Monocytes, Killer Cells, Natural, Animals, Simian Immunodeficiency Virus, Signal Transduction
Abstract

Deglycosylated, live-attenuated SIV vaccines elicited protective immune responses against heterologous SIVsmE543–3, which differs from the vaccine strain SIVmac239 to levels similar to those across HIV-1 clades. 2/3 of the vaccinees contained the chronic SIVsmE543–3 infection (controllers), whereas 1/3 did not (non-controllers). In this study, we investigated immune correlates of heterologous challenge control in rhesus macaques of Burmese origin. Since depletion of CD8+ cells in the controllers by administration of anti-CD8α antibody abrogated the control of viral replication, CD8+ cells were required for the protective immune response. However, classical SIV specific CD8+ T cells did not account for the protective immune response in all controllers. Instead, IL-15 responding CD8α+ cells, including CD8+ T and NK cells, were significantly higher in the controllers than those in the non-controllers, before and after vaccination with deglycosylated SIV. It is well established that IL-15 signal transduction occurs through “trans-presentation” in which IL-15 complexed with IL-15Rα on monocytes, macrophages and dendritic cells binds to IL-15 Rβ/γ expressed on CD8+ T and NK cells. Accordingly, levels of IL-15 stimulation was strongly affected by the depletion of monocytes from PBMCs, implying key roles of innate immune cells. These results suggest that intrinsic IL-15 responsiveness may dictate the outcome of protective responses and may lead to optimized formulations of future broadly protective HIV vaccines.

Published
2020

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