ImmunoHorizons最新文献

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Air Pollution Drives Macrophage Senescence through a Phagolysosome-15-Lipoxygenase Pathway. 空气污染通过吞噬溶酶体-15-脂氧合酶途径促使巨噬细胞衰老
ImmunoHorizons Pub Date : 2024-04-01 DOI: 10.4049/immunohorizons.2300096
Sarah A Thomas, H. Yong, Ana M Rule, N. Gour, Stephane Lajoie
{"title":"Air Pollution Drives Macrophage Senescence through a Phagolysosome-15-Lipoxygenase Pathway.","authors":"Sarah A Thomas, H. Yong, Ana M Rule, N. Gour, Stephane Lajoie","doi":"10.4049/immunohorizons.2300096","DOIUrl":"https://doi.org/10.4049/immunohorizons.2300096","url":null,"abstract":"Urban particulate matter (PM; uPM) poses significant health risks, particularly to the respiratory system. Fine particles, such as PM2.5, can penetrate deep into the lungs and exacerbate a range of health problems, including emphysema, asthma, and lung cancer. PM exposure is also linked to extrapulmonary disorders such as heart and neurodegenerative diseases. Moreover, prolonged exposure to elevated PM levels can reduce overall life expectancy. Senescence is a dysfunctional cell state typically associated with age but can also be precipitated by environmental stressors. This study aimed to determine whether uPM could drive senescence in macrophages, an essential cell type involved in particulate phagocytosis-mediated clearance. Although it is known that uPM exposure impairs immune function, this deficit is multifaceted and incompletely understood, partly because of the use of particulates such as diesel exhaust particles as a surrogate for true uPM. uPM was collected from several locations in the United States, including Baltimore, Houston, and Phoenix. Bone marrow-derived macrophages were stimulated with uPM or reference particulates (e.g., diesel exhaust particles) to assess senescence-related parameters. We report that uPM-exposed bone marrow-derived macrophages adopt a senescent phenotype characterized by increased IL-1α secretion, senescence-associated β-galactosidase activity, and diminished proliferation. Exposure to allergens failed to elicit such a response, supporting a distinction between different types of environmental exposure. uPM-induced senescence was independent of key macrophage activation pathways, specifically inflammasome and scavenger receptors. However, inhibition of the phagolysosome pathway abrogated senescence markers, supporting this phenotype's attribution to uPM phagocytosis. These data suggest that uPM exposure leads to macrophage senescence, which may contribute to immunopathology.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"145 ","pages":"307-316"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140767739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IL-17RA-Mediated Epithelial Cell Activity Prevents Severe Inflammatory Response to Helicobacter pylori Infection. IL-17RA介导的上皮细胞活性可预防幽门螺旋杆菌感染引起的严重炎症反应
ImmunoHorizons Pub Date : 2024-04-01 DOI: 10.4049/immunohorizons.2300078
Lee C. Brackman, Matthew S. Jung, Eseoghene I Ogaga, Nikhita Joshi, Lydia E. Wroblewski, M. Piazuelo, R. Peek, Y. Choksi, H. Algood
{"title":"IL-17RA-Mediated Epithelial Cell Activity Prevents Severe Inflammatory Response to Helicobacter pylori Infection.","authors":"Lee C. Brackman, Matthew S. Jung, Eseoghene I Ogaga, Nikhita Joshi, Lydia E. Wroblewski, M. Piazuelo, R. Peek, Y. Choksi, H. Algood","doi":"10.4049/immunohorizons.2300078","DOIUrl":"https://doi.org/10.4049/immunohorizons.2300078","url":null,"abstract":"Helicobacter pylori is a Gram-negative pathogen that colonizes the stomach, induces inflammation, and drives pathological changes in the stomach tissue, including gastric cancer. As the principal cytokine produced by Th17 cells, IL-17 mediates protective immunity against pathogens by inducing the activation and mobilization of neutrophils. Whereas IL-17A is largely produced by lymphocytes, the IL-17 receptor is expressed in epithelial cells, fibroblasts, and hematopoietic cells. Loss of the IL-17RA in mice results in impaired antimicrobial responses to extracellular bacteria. In the context of H. pylori infection, this is compounded by extensive inflammation in Il17ra-/- mice. In this study, Foxa3creIl17rafl/fl (Il17raΔGI-Epi) and Il17rafl/fl (control) mice were used to test the hypothesis that IL-17RA signaling, specifically in epithelial cells, protects against severe inflammation after H. pylori infection. The data indicate that Il17raΔGI-Epi mice develop increased inflammation compared with controls. Despite reduced Pigr expression, levels of IgA increased in the gastric wash, suggesting significant increase in Ag-specific activation of the T follicular helper/B cell axis. Gene expression analysis of stomach tissues indicate that both acute and chronic responses are significantly increased in Il17raΔGI-Epi mice compared with controls. These data suggest that a deficiency of IL-17RA in epithelial cells is sufficient to drive chronic inflammation and hyperactivation of the Th17/T follicular helper/B cell axis but is not required for recruitment of polymorphonuclear neutrophils. Furthermore, the data suggest that fibroblasts can produce chemokines in response to IL-17 and may contribute to H. pylori-induced inflammation through this pathway.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"55 42","pages":"339-353"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monophosphoryl Lipid A-based Adjuvant to Promote the Immunogenicity of Multivalent Meningococcal Polysaccharide Conjugate Vaccines. 基于单磷脂 A 的佐剂提高多价脑膜炎球菌多糖结合疫苗的免疫原性
ImmunoHorizons Pub Date : 2024-04-01 DOI: 10.4049/immunohorizons.2400013
K. Alugupalli
{"title":"Monophosphoryl Lipid A-based Adjuvant to Promote the Immunogenicity of Multivalent Meningococcal Polysaccharide Conjugate Vaccines.","authors":"K. Alugupalli","doi":"10.4049/immunohorizons.2400013","DOIUrl":"https://doi.org/10.4049/immunohorizons.2400013","url":null,"abstract":"Activation of the adaptive immune system requires the engagement of costimulatory pathways in addition to B and T cell Ag receptor signaling, and adjuvants play a central role in this process. Many Gram-negative bacterial polysaccharide vaccines, including the tetravalent meningococcal conjugate vaccines (MCV4) and typhoid Vi polysaccharide vaccines, do not incorporate adjuvants. The immunogenicity of typhoid vaccines is due to the presence of associated TLR4 ligands in these vaccines. Because the immunogenicity of MCV4 is poor and requires boosters, I hypothesized that TLR4 ligands are absent in MCV4 and that incorporation of a TLR4 ligand-based adjuvant would improve their immunogenicity. Consistent with this hypothesis, two Food and Drug Administration-approved MCV4 vaccines, MENVEO and MenQuadfi, lack TLR4 ligands. Admixing monophosphoryl lipid A, a TLR4 ligand-based adjuvant formulation named \"Turbo\" with MCV4 induced significantly improved IgM and IgG responses to all four meningococcal serogroup polysaccharides in adult and aged mice after a single immunization. Furthermore, in infant mice, a single booster was sufficient to promote a robust IgG response and 100% seroconversion when MCV4 was adjuvanted with Turbo. Turbo upregulated the expression of the costimulatory molecules CD40 and CD86 on B cells, and Turbo-driven adjuvanticity is lost in mice deficient in CD40 and CD86. These data suggest that Turbo induces the required costimulatory molecules for its adjuvant activity and that incorporation of Turbo could make bacterial polysaccharide vaccines more immunogenic, minimize booster requirements, and be cost-effective, particularly for those individuals in low- and middle-income and disease-endemic countries.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"179 12","pages":"317-325"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TCF1highPD-1+Ly108+CD8+ T Cells Are Associated with Graft Preservation in Sensitized Mice Treated with Non-Fc Receptor-Binding CD3 Antibodies. TCF1highPD-1+Ly108+CD8+ T 细胞与非 Fc 受体结合型 CD3 抗体治疗致敏小鼠的移植物保存有关。
ImmunoHorizons Pub Date : 2024-04-01 DOI: 10.4049/immunohorizons.2300117
Takuji Ota, R. Goto, Takuya Harada, Agustina Forgioni, Ryo Kanazawa, Yoshikazu Ganchiku, N. Kawamura, Masaaki Watanabe, M. Fukai, Tsuyoshi Shimamura, A. Taketomi
{"title":"TCF1highPD-1+Ly108+CD8+ T Cells Are Associated with Graft Preservation in Sensitized Mice Treated with Non-Fc Receptor-Binding CD3 Antibodies.","authors":"Takuji Ota, R. Goto, Takuya Harada, Agustina Forgioni, Ryo Kanazawa, Yoshikazu Ganchiku, N. Kawamura, Masaaki Watanabe, M. Fukai, Tsuyoshi Shimamura, A. Taketomi","doi":"10.4049/immunohorizons.2300117","DOIUrl":"https://doi.org/10.4049/immunohorizons.2300117","url":null,"abstract":"The non-Fc-binding anti-CD3 Ab [anti-CD3F(ab')2] can induce graft acceptance depending on the therapeutic window in a rodent heart transplant model. The delayed protocol allows for early graft infiltration of lymphocytes, which may behave in an inhibitory manner. We investigated the most effective protocol for anti-CD3F(ab')2 in sensitized conditions to confirm the evidence for clinical application. C57BL/6 mice were sensitized with BALB/c tail skin grafts and transplanted with BALB/c heart grafts at 8-12 wk after sensitization. Fifty micrograms of anti-CD3F(ab')2 was administered daily for 5 consecutive days on days 1-5 (day 1 protocol) or days 3-7 (delayed protocol). In nonsensitized mice, the delayed protocol significantly prolonged graft survival after transplantation from BALB/c to naive B6 (median survival time [MST], >100 d). In contrast, the delayed protocol was unable to prevent graft rejection in sensitized mice (MST, 5 d). A significantly increased percentage of granzyme B+ CD8+ T cells was observed in the graft on day 3 posttransplantation in sensitized conditions. Further, the day 1 protocol significantly prolonged graft survival (MST, 18 d), even in sensitized conditions. Day 1 treatment significantly increased the percentage of Foxp3+CD25+CD4+ T cells and phenotypically changed CD8+ T cells in the graft (i.e., caused a significant increase in the proportion of Ly108+TCF1highPD-1+CD8+ T cells). In conclusion, different timings of delayed anti-CD3F(ab')2 treatment promoted allograft preservation in association with phenotypic changes in CD4+ and CD8+ T cells in the graft under sensitized conditions.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"105 7","pages":"295-306"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Membership Has Its Privileges. 会员有特权
ImmunoHorizons Pub Date : 2024-04-01 DOI: 10.4049/immunohorizons.2400035
Mark H Kaplan
{"title":"Membership Has Its Privileges.","authors":"Mark H Kaplan","doi":"10.4049/immunohorizons.2400035","DOIUrl":"https://doi.org/10.4049/immunohorizons.2400035","url":null,"abstract":"","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 4","pages":"354"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11066710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions. 基于近距离标记的 MHC II 类和 CD37 是具有免疫功能的 B 细胞受体近端蛋白。
ImmunoHorizons Pub Date : 2024-04-01 DOI: 10.4049/immunohorizons.2400014
Sean Hoeger, Lisa A. Drake, J. Drake
{"title":"Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions.","authors":"Sean Hoeger, Lisa A. Drake, J. Drake","doi":"10.4049/immunohorizons.2400014","DOIUrl":"https://doi.org/10.4049/immunohorizons.2400014","url":null,"abstract":"The BCR allows for Ag-driven B cell activation and subsequent Ag endocytosis, processing, and presentation to recruit T cell help. Core drivers of BCR signaling and endocytosis are motifs within the receptor's cytoplasmic tail (primarily CD79). However, BCR function can be tuned by other proximal cellular elements, such as CD20 and membrane lipid microdomains. To identify additional proteins that could modulate BCR function, we used a proximity-based biotinylation technique paired with mass spectrometry to identify molecular neighbors of the murine IgM BCR. Those neighbors include MHC class II molecules, integrins, various transporters, and membrane microdomain proteins. Class II molecules, some of which are invariant chain-associated nascent class II, are a readily detected BCR neighbor. This finding is consistent with reports of BCR-class II association within intracellular compartments. The BCR is also in close proximity to multiple proteins involved in the formation of membrane microdomains, including CD37, raftlin, and Ig superfamily member 8. Known defects in T cell-dependent humoral immunity in CD37 knockout mice suggest a role for CD37 in BCR function. In line with this notion, CRISPR-based knockout of CD37 expression in a B cell line heightens BCR signaling, slows BCR endocytosis, and tempers formation of peptide-class II complexes. These results indicate that BCR molecular neighbors can impact membrane-mediated BCR functions. Overall, a proximity-based labeling technique allowed for identification of multiple previously unknown BCR molecular neighbors, including the tetraspanin protein CD37, which can modulate BCR function.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"114 ","pages":"326-338"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
On Rats with Oversized Genitalia and Other Submissions. 关于生殖器过大的老鼠和其他呈文。
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2400020
Mark H Kaplan
{"title":"On Rats with Oversized Genitalia and Other Submissions.","authors":"Mark H Kaplan","doi":"10.4049/immunohorizons.2400020","DOIUrl":"10.4049/immunohorizons.2400020","url":null,"abstract":"","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"227"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Embigin Is Highly Expressed on CD4+ and CD8+ T Cells but Is Dispensable for Several T Cell Effector Responses. Embigin在CD4+和CD8+T细胞上高表达,但在几种T细胞效应反应中是不可或缺的。
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300083
Haoran Yang, Naoki Iwanaga, Alexis R Katz, Andy R Ridley, Haiyan D Miller, Michaela J Allen, Dereck Pociask, Jay K Kolls
{"title":"Embigin Is Highly Expressed on CD4+ and CD8+ T Cells but Is Dispensable for Several T Cell Effector Responses.","authors":"Haoran Yang, Naoki Iwanaga, Alexis R Katz, Andy R Ridley, Haiyan D Miller, Michaela J Allen, Dereck Pociask, Jay K Kolls","doi":"10.4049/immunohorizons.2300083","DOIUrl":"10.4049/immunohorizons.2300083","url":null,"abstract":"<p><p>T cell immunity, including CD4+ and CD8+ T cell immunity, is critical to host immune responses to infection. Transcriptomic analyses of both CD4+ and CD8+ T cells of C57BL/6 mice show high expression the gene encoding embigin, Emb, which encodes a transmembrane glycoprotein. Moreover, we found that lung CD4+ Th17 tissue-resident memory T cells of C57BL/6 mice also express high levels of Emb. However, deletion of Emb in αβ T cells of C57BL/6 mice revealed that Emb is dispensable for thymic T cell development, generation of lung Th17 tissue-resident memory T cells, tissue-resident memory T cell homing to the lung, experimental autoimmune encephalitis, as well as clearance of pulmonary viral or fungal infection. Thus, based on this study, embigin appears to play a minor role if any in αβ T cell development or αβ T cell effector functions in C57BL/6 mice.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"242-253"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease. 脂肪酸在移植物抗宿主疾病效应 T 细胞线粒体氧化磷酸化过程中发挥关键作用
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300115
Hirofumi Nakano, Kazuya Sato, Junko Izawa, Norihito Takayama, Hiroko Hayakawa, Takashi Ikeda, Shin-Ichiro Kawaguchi, Kiyomi Mashima, Kento Umino, Kaoru Morita, Ryoji Ito, Nobuhiko Ohno, Kaoru Tominaga, Hitoshi Endo, Yoshinobu Kanda
{"title":"Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease.","authors":"Hirofumi Nakano, Kazuya Sato, Junko Izawa, Norihito Takayama, Hiroko Hayakawa, Takashi Ikeda, Shin-Ichiro Kawaguchi, Kiyomi Mashima, Kento Umino, Kaoru Morita, Ryoji Ito, Nobuhiko Ohno, Kaoru Tominaga, Hitoshi Endo, Yoshinobu Kanda","doi":"10.4049/immunohorizons.2300115","DOIUrl":"10.4049/immunohorizons.2300115","url":null,"abstract":"<p><p>Although the role of aerobic glycolysis in activated T cells has been well characterized, whether and how fatty acids (FAs) contribute to donor T cell function in allogeneic hematopoietic stem cell transplantation is unclear. Using xenogeneic graft-versus-host disease (GVHD) models, this study demonstrated that exogenous FAs serve as a crucial source of mitochondrial respiration in donor T cells in humans. By comparing human T cells isolated from wild-type NOD/Shi-scid-IL2rγnull (NOG) mice with those from MHC class I/II-deficient NOG mice, we found that donor T cells increased extracellular FA uptake, the extent of which correlates with their proliferation, and continued to increase FA uptake during effector differentiation. Gene expression analysis showed the upregulation of a wide range of lipid metabolism-related genes, including lipid hydrolysis, mitochondrial FA transport, and FA oxidation. Extracellular flux analysis demonstrated that mitochondrial FA transport was required to fully achieve the mitochondrial maximal respiration rate and spare respiratory capacity, whereas the substantial disruption of glucose supply by either glucose deprivation or mitochondrial pyruvate transport blockade did not impair oxidative phosphorylation. Taken together, FA-driven mitochondrial respiration is a hallmark that differentiates TCR-dependent T cell activation from TCR-independent immune response after hematopoietic stem cell transplant.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"228-241"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3. 炭疽杆菌的肽聚糖部分通过降低细胞表面 MERTK 和 TIM-3 的表达抑制人类巨噬细胞的吞噬作用
ImmunoHorizons Pub Date : 2024-03-01 DOI: 10.4049/immunohorizons.2300109
Joshua S Mytych, Zijian Pan, Charmaine Lopez-Davis, Nancy Redinger, Christina Lawrence, Jadith Ziegler, Narcis I Popescu, Judith A James, A Darise Farris
{"title":"Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3.","authors":"Joshua S Mytych, Zijian Pan, Charmaine Lopez-Davis, Nancy Redinger, Christina Lawrence, Jadith Ziegler, Narcis I Popescu, Judith A James, A Darise Farris","doi":"10.4049/immunohorizons.2300109","DOIUrl":"10.4049/immunohorizons.2300109","url":null,"abstract":"<p><p>Bacillus anthracis peptidoglycan (PGN) is a major component of the bacterial cell wall and a key pathogen-associated molecular pattern contributing to anthrax pathology, including organ dysfunction and coagulopathy. Increases in apoptotic leukocytes are a late-stage feature of anthrax and sepsis, suggesting there is a defect in apoptotic clearance. In this study, we tested the hypothesis that B. anthracis PGN inhibits the capacity of human monocyte-derived macrophages (MΦ) to efferocytose apoptotic cells. Exposure of CD163+CD206+ MΦ to PGN for 24 h impaired efferocytosis in a manner dependent on human serum opsonins but independent of complement component C3. PGN treatment reduced cell surface expression of the proefferocytic signaling receptors MERTK, TYRO3, AXL, integrin αVβ5, CD36, and TIM-3, whereas TIM-1, αVβ3, CD300b, CD300f, STABILIN-1, and STABILIN-2 were unaffected. ADAM17 is a major membrane-bound protease implicated in mediating efferocytotic receptor cleavage. We found multiple ADAM17-mediated substrates increased in PGN-treated supernatant, suggesting involvement of membrane-bound proteases. ADAM17 inhibitors TAPI-0 and Marimastat prevented TNF release, indicating effective protease inhibition, and modestly increased cell-surface levels of MerTK and TIM-3 but only partially restored efferocytic capacity by PGN-treated MΦ. We conclude that human serum factors are required for optimal recognition of PGN by human MΦ and that B. anthracis PGN inhibits efferocytosis in part by reducing cell surface expression of MERTK and TIM-3.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 3","pages":"269-280"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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