Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice
Summary: Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by interferon (IFN)-γ-producing immature myeloid cells (γIMCs), which are selectively r...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719303869 |
| _version_ | 1811238205491511296 |
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| author | Takayuki Matsumura Tadayoshi Ikebe Koji Arikawa Masahito Hosokawa Michio Aiko Aoi Iguchi Ikuko Togashi Sayaka Kai Sakiko Ohara Naoya Ohara Makoto Ohnishi Haruo Watanabe Kazuo Kobayashi Haruko Takeyama Sho Yamasaki Yoshimasa Takahashi Manabu Ato |
| author_facet | Takayuki Matsumura Tadayoshi Ikebe Koji Arikawa Masahito Hosokawa Michio Aiko Aoi Iguchi Ikuko Togashi Sayaka Kai Sakiko Ohara Naoya Ohara Makoto Ohnishi Haruo Watanabe Kazuo Kobayashi Haruko Takeyama Sho Yamasaki Yoshimasa Takahashi Manabu Ato |
| author_sort | Takayuki Matsumura |
| collection | DOAJ |
| description | Summary: Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by interferon (IFN)-γ-producing immature myeloid cells (γIMCs), which are selectively recruited upon severe invasive GAS infection in mice. Here, we demonstrate that γIMCs provide this IFN-γ-mediated protection by sequentially sensing GAS through two distinct pattern recognition receptors. In a mouse model, GAS is initially recognized by Toll-like receptor 2 (TLR2), which promptly induces interleukin (IL)-6 production in γIMCs. γIMC-derived IL-6 promotes the upregulation of a recently identified GAS-sensing receptor, macrophage-inducible C-type lectin (Mincle), in an autocrine or paracrine manner. Notably, blockade of γIMC-derived IL-6 abrogates Mincle expression, downstream IFN-γ production, and γIMC-mediated protection against severe invasive GAS infection. Thus, γIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2–IL-6–Mincle axis. : Matsumura et al. show that γIMCs sequentially sense group A Streptococcus (GAS) through TLR2 and Mincle. Specifically, TLR2-triggered production of IL-6 functions as an intermediate that amplifies Mincle expression to maximize host protection through IFN-γ production. The sequential sensing is a distinct feature in γIMCs following severe invasive GAS infection. Keywords: group A Streptococcus infections, immature myeloid cells, Toll-like receptors, C-type lectin receptors, cytokines |
| first_indexed | 2024-04-12T12:37:51Z |
| format | Article |
| id | doaj.art-c50eebe37130461e86dfae29f91fefcc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T12:37:51Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c50eebe37130461e86dfae29f91fefcc2022-12-22T03:32:52ZengElsevierCell Reports2211-12472019-04-01272561571.e6Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in MiceTakayuki Matsumura0Tadayoshi Ikebe1Koji Arikawa2Masahito Hosokawa3Michio Aiko4Aoi Iguchi5Ikuko Togashi6Sayaka Kai7Sakiko Ohara8Naoya Ohara9Makoto Ohnishi10Haruo Watanabe11Kazuo Kobayashi12Haruko Takeyama13Sho Yamasaki14Yoshimasa Takahashi15Manabu Ato16Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Corresponding authorDepartment of Bacteriology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, JapanResearch Organization for Nano and Life Innovation, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan; Computational Bio Big-Data Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, JapanResearch Organization for Nano and Life Innovation, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan; Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, JapanDepartment of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, JapanDepartment of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Tokyo College of Biotechnology, 1-3-14 Kita-Kojiya, Ota-ku, Tokyo 144-0032, JapanDepartment of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Tokyo College of Biotechnology, 1-3-14 Kita-Kojiya, Ota-ku, Tokyo 144-0032, JapanDepartment of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Dental School, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, JapanDepartment of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Dental School, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, JapanDental School, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan; Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, JapanDepartment of Bacteriology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, JapanSchool of Medicine, International University of Health and Welfare, 4-3 Kozunomori, Narita-shi, Chiba 286-8686, JapanDivision of Public Health, Osaka Institute of Public Health, 1-3-69 Nakamichi, Higashinari-ku, Osaka-shi, Osaka 537-0025, JapanResearch Organization for Nano and Life Innovation, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan; Computational Bio Big-Data Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan; Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, JapanDivision of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan; Division of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita-shi, Osaka 565-0871, JapanDepartment of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, JapanDepartment of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama-shi, Tokyo 189-0002, JapanSummary: Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by interferon (IFN)-γ-producing immature myeloid cells (γIMCs), which are selectively recruited upon severe invasive GAS infection in mice. Here, we demonstrate that γIMCs provide this IFN-γ-mediated protection by sequentially sensing GAS through two distinct pattern recognition receptors. In a mouse model, GAS is initially recognized by Toll-like receptor 2 (TLR2), which promptly induces interleukin (IL)-6 production in γIMCs. γIMC-derived IL-6 promotes the upregulation of a recently identified GAS-sensing receptor, macrophage-inducible C-type lectin (Mincle), in an autocrine or paracrine manner. Notably, blockade of γIMC-derived IL-6 abrogates Mincle expression, downstream IFN-γ production, and γIMC-mediated protection against severe invasive GAS infection. Thus, γIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2–IL-6–Mincle axis. : Matsumura et al. show that γIMCs sequentially sense group A Streptococcus (GAS) through TLR2 and Mincle. Specifically, TLR2-triggered production of IL-6 functions as an intermediate that amplifies Mincle expression to maximize host protection through IFN-γ production. The sequential sensing is a distinct feature in γIMCs following severe invasive GAS infection. Keywords: group A Streptococcus infections, immature myeloid cells, Toll-like receptors, C-type lectin receptors, cytokineshttp://www.sciencedirect.com/science/article/pii/S2211124719303869 |
| spellingShingle | Takayuki Matsumura Tadayoshi Ikebe Koji Arikawa Masahito Hosokawa Michio Aiko Aoi Iguchi Ikuko Togashi Sayaka Kai Sakiko Ohara Naoya Ohara Makoto Ohnishi Haruo Watanabe Kazuo Kobayashi Haruko Takeyama Sho Yamasaki Yoshimasa Takahashi Manabu Ato Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice Cell Reports |
| title | Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice |
| title_full | Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice |
| title_fullStr | Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice |
| title_full_unstemmed | Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice |
| title_short | Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice |
| title_sort | sequential sensing by tlr2 and mincle directs immature myeloid cells to protect against invasive group a streptococcal infection in mice |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719303869 |
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