{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:11:15Z","timestamp":1794006675088,"version":"4.8.0"},"reference-count":92,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"The National Research Council of Thailand","doi-asserted-by":"crossref","award":["N84A680764"],"award-info":[{"award-number":["N84A680764"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004704","name":"The National Research Council of Thailand","doi-asserted-by":"crossref","award":["N32A680647"],"award-info":[{"award-number":["N32A680647"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004704","name":"The National Research Council of Thailand","doi-asserted-by":"crossref","award":["N42A680063"],"award-info":[{"award-number":["N42A680063"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University","award":["RA-MF-18\/65"],"award-info":[{"award-number":["RA-MF-18\/65"]}]},{"name":"Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University","award":["RA-MF 15\/66"],"award-info":[{"award-number":["RA-MF 15\/66"]}]},{"name":"Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University","award":["RA-MF 14\/67"],"award-info":[{"award-number":["RA-MF 14\/67"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Activation of cGAS, a receptor recognizing cytosolic DNA, in macrophages might be associated with rabies (an RNA virus) through mitochondrial damage. A similar mortality rate was observed between cGAS-deficient (cGAS-\/-) and wild-type (WT) mice post-CVS-11 strain injection. However, 2 out of 12 cGAS-\/- mice (but not WT) survived for 15 days post-injection. At 7 days post-infection, less severe brain inflammation in cGAS-\/- mice was demonstrated by the viral abundance in the hippocampus, the expression of proinflammatory genes (TNF-\u03b1 and IL-1\u03b2), and the Evans blue dye assay (blood\u2013brain barrier defect) with the presence of higher anti-inflammatory genes (TGF-\u03b2 and arginase-1). Fecal Proteobacteria was more prominent in the infected WT mice, while serum cytokines (TNF-\u03b1 and IL-1\u03b2) were similar in both mouse strains. There were less prominent responses against the rabies virus in cGAS-\/- macrophages than in WT cells, as indicated by supernatant IL-6 and the gene expression of TLR-3, RIG-1, MDA-5, and iNOS. On the other hand, mitochondrial injury and cGAS activation were more prominent in WT macrophages over cGAS-\/- cells, as indicated by cGAS expression, supernatant cGAMP (a secondary messenger of cGAS), and mitochondrial oxidative stress (MitoSox) together with a decrease in mitochondrial DNA and maximal respiration (extracellular flux analysis). In conclusion, (i) rabies-damaged mitochondria led to cGAS activation that was less severe in cGAS-\/- than in WT, (ii) rabies-induced dysbiosis was demonstrated, and (iii) cGAS manipulation and gut\u2013brain axis-associated inflammation warrants further investigation.<\/jats:p>","DOI":"10.3390\/biology14111583","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:10:45Z","timestamp":1763025045000},"page":"1583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Less Severe Inflammation in Cyclic GMP\u2013AMP Synthase (cGAS)-Deficient Mice with Rabies, Impact of Mitochondrial Injury, and Gut\u2013Brain Axis"],"prefix":"10.3390","volume":"14","author":[{"given":"Pannatat","family":"Areekul","sequence":"first","affiliation":[{"name":"Department of Research and Development, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thansita","family":"Bhunyakarnjanarat","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakolwan","family":"Suebnuson","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4504-9564","authenticated-orcid":false,"given":"Kollawat","family":"Somsri","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Chulalongkorn University International Medical Program (CU-MEDi), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somchanok","family":"Trakultritrung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Taveethavornsawat","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4177-2165","authenticated-orcid":false,"given":"Tewin","family":"Tencomnao","sequence":"additional","affiliation":[{"name":"Center of Excellence on Natural Products for Neuroprotection and Anti-Ageing (Neur-Age Natura), Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-3573","authenticated-orcid":false,"given":"Siwaporn","family":"Boonyasuppayakorn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5566-6403","authenticated-orcid":false,"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101102","DOI":"10.1016\/j.onehlt.2025.101102","article-title":"Incidence and prevalence of rabies virus infections in tested humans and animals in Asia: A systematic review and meta-analysis study","volume":"20","author":"Shams","year":"2025","journal-title":"One Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s40506-024-00280-3","article-title":"Human Rabies: Laboratory Diagnosis, Management and Nanomedicine","volume":"17","author":"Pattiyakumbura","year":"2024","journal-title":"Curr. Treat. Options Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/ame2.12273","article-title":"Regulation of innate immune responses by rabies virus","volume":"5","author":"Zhang","year":"2022","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Conzelmann, K.-K. (2015). Activation and evasion of innate immune response by rhabdoviruses. Biology and Pathogenesis of Rhabdo-and Filoviruses, World Scientific.","DOI":"10.1142\/9789814635349_0015"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wu, D., Wang, J., Huang, C., Zhao, J., Fu, Z.F., Zhao, L., and Zhou, M. (2023). Interleukin-1\u03b2 suppresses rabies virus infection by activating cGAS-STING pathway and compromising the blood-brain barrier integrity in mice. Vet. Microbiol., 280.","DOI":"10.1016\/j.vetmic.2023.109708"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Riedel, C., Hennrich, A.A., and Conzelmann, K.K. (2020). Components and Architecture of the Rhabdovirus Ribonucleoprotein Complex. Viruses, 12.","DOI":"10.3390\/v12090959"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kiflu, A.B. (2024). The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms. Viruses, 16.","DOI":"10.3390\/v16111774"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Fang, A., Wang, H., Wang, C., Sui, B., Zhao, J., Fu, Z.F., Zhou, M., and Zhao, L. (2024). Lyssavirus M protein degrades neuronal microtubules by reprogramming mitochondrial metabolism. mBio, 15.","DOI":"10.1128\/mbio.02880-23"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11801","DOI":"10.1128\/JVI.79.18.11801-11812.2005","article-title":"Rabies virus-induced activation of mitogen-activated protein kinase and NF-kappaB signaling pathways regulates expression of CXC and CC chemokine ligands in microglia","volume":"79","author":"Nakamichi","year":"2005","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, Y., He, H., Li, J., Chen, L., Luo, J., Kuang, Y., Lv, Z., Fan, R., Zhang, B., and Luo, Y. (2021). Rabies Virus-Induced Autophagy Is Dependent on Viral Load in BV2 Cells. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.595678"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s007050050136","article-title":"Rabies viruses infect primary cultures of murine, feline, and human microglia and astrocytes","volume":"142","author":"Ray","year":"1997","journal-title":"Arch. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tins.2021.11.004","article-title":"Beneficial and detrimental functions of microglia during viral encephalitis","volume":"45","author":"Waltl","year":"2022","journal-title":"Trends Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00018-025-05580-5","article-title":"Double-stranded RNA orbivirus disrupts the DNA-sensing cGAS-sting axis to prevent type I IFN induction","volume":"82","author":"Rojas","year":"2025","journal-title":"Cell Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ni, G., Ma, Z., and Damania, B. (2018). cGAS and STING: At the intersection of DNA and RNA virus-sensing networks. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007148"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s13365-015-0320-8","article-title":"Rabies virus phosphoprotein interacts with mitochondrial Complex I and induces mitochondrial dysfunction and oxidative stress","volume":"21","author":"Kammouni","year":"2015","journal-title":"J. Neurovirol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.chom.2016.07.008","article-title":"Dengue Virus Perturbs Mitochondrial Morphodynamics to Dampen Innate Immune Responses","volume":"20","author":"Cortese","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ahmed, S., Varga, R.D., and Yang, J. (2025). The Impacts of Dengue Virus Infection on Mitochondrial Functions and Dynamics. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26188968"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/eji.201344127","article-title":"Recognition of cytosolic DNA by cGAS and other STING-dependent sensors","volume":"44","author":"Bhat","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41577-018-0117-0","article-title":"DNA-stimulated cell death: Implications for host defence, inflammatory diseases and cancer","volume":"19","author":"Paludan","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","first-page":"28","article-title":"The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health","volume":"17","author":"Appleton","year":"2018","journal-title":"Integr. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Niu, L., Gao, M., Wen, S., Wang, F., Shangguan, H., Guo, Z., Zhang, R., and Ge, J. (2023). Effects of Catecholamine Stress Hormones Norepinephrine and Epinephrine on Growth, Antimicrobial Susceptibility, Biofilm Formation, and Gene Expressions of Enterotoxigenic Escherichia coli. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115646"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.00826-16","article-title":"Bacterial Adrenergic Sensors Regulate Virulence of Enteric Pathogens in the Gut","volume":"7","author":"Moreira","year":"2016","journal-title":"mBio"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1128\/AEM.00075-06","article-title":"Enhancement of in vitro growth of pathogenic bacteria by norepinephrine: Importance of inoculum density and role of transferrin","volume":"72","author":"Aviles","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1042\/CS20220777","article-title":"The leaky gut and the gut microbiome in sepsis \u2014Targets in research and treatment","volume":"137","author":"Chancharoenthana","year":"2023","journal-title":"Clin. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1093\/cid\/ciae581","article-title":"Noninferiority Study of Purified Vero Rabies Vaccine\u2014Serum Free in 3-dose and 2-dose Preexposure Prophylaxis Regimens in Comparison With Licensed Rabies Vaccines","volume":"81","author":"Chokephaibulkit","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/SHK.0000000000001473","article-title":"Plasma miR-370-3P as a Biomarker of Sepsis-Associated Encephalopathy, the Transcriptomic Profiling Analysis of Microrna-Arrays From Mouse Brains","volume":"54","author":"Visitchanakun","year":"2020","journal-title":"Shock"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Thim-Uam, A., Makjaroen, J., Issara-Amphorn, J., Saisorn, W., Wannigama, D.L., Chancharoenthana, W., and Leelahavanichkul, A. (2022). Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031676"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chancharoenthana, W., Kamolratanakul, S., Udompornpitak, K., Wannigama, D.L., Schultz, M.J., and Leelahavanichkul, A. (2025). Alcohol-induced gut permeability defect through dysbiosis and enterocytic mitochondrial interference causing pro-inflammatory macrophages in a dose dependent manner. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-97593-0"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1042\/CS20210328","article-title":"Increased susceptibility to dextran sulfate-induced mucositis of iron-overload \u03b2-thalassemia mice, another endogenous cause of septicemia in thalassemia","volume":"135","author":"Visitchanakun","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ondee, T., Pongpirul, K., Wongsaroj, L., Senaprom, S., Wattanaphansak, S., and Leelahavanichkul, A. (2025). Lactiplantibacillus plantarum dfa1 reduces obesity caused by a high carbohydrate diet by modulating inflammation and gut microbiota. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-10435-x"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00011-025-02036-1","article-title":"Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization","volume":"74","author":"Chantawichitwong","year":"2025","journal-title":"Inflamm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41592-022-01520-4","article-title":"Emu: Species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data","volume":"19","author":"Curry","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hiengrach, P., Visitchanakun, P., Finkelman, M.A., Chancharoenthana, W., and Leelahavanichkul, A. (2022). More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-\u03b2-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074026"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000526206","article-title":"Obesity Exacerbates Lupus Activity in Fc Gamma Receptor IIb Deficient Lupus Mice Partly through Saturated Fatty Acid-Induced Gut Barrier Defect and Systemic Inflammation","volume":"15","author":"Udompornpitak","year":"2023","journal-title":"J. Innate Immun."},{"key":"ref_35","unstructured":"Bhunyakarnjanarat, T., Prapunwatana, P., Tiranathanagul, K., and Leelahavanichkul, A. (2023). Determination of the number of times for reuse of hemodialysis dialyzer through macrophage responses against dialyzer-eluted protein, a proposed method. Asian Pac. J. Allergy Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Suksamai, C., Kaewduangduen, W., Phuengmaung, P., Sae-Khow, K., Charoensappakit, A., Udomkarnjananun, S., Lotinun, S., Kueanjinda, P., and Leelahavanichkul, A. (2025). Cyclic GMP-AMP Synthase (cGAS) Deletion Promotes Less Prominent Inflammatory Macrophages and Sepsis Severity in Catheter-Induced Infection and LPS Injection Models. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115069"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Suksawad, N., Udompornpitak, K., Thawinpipat, N., Korwattanamongkol, P., Visitchanakun, P., Phuengmaung, P., Saisorn, W., Kueanjinda, P., and Leelahavanichkul, A. (2023). Cyclic GMP-AMP Synthase (cGAS) Deletion Reduces Severity in Bilateral Nephrectomy Mice through Changes in Neutrophil Extracellular Traps and Mitochondrial Respiration. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041208"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Visitchanakun, P., Kaewduangduen, W., Chareonsappakit, A., Susantitaphong, P., Pisitkun, P., Ritprajak, P., Townamchai, N., and Leelahavanichkul, A. (2021). Interference on Cytosolic DNA Activation Attenuates Sepsis Severity: Experiments on Cyclic GMP-AMP Synthase (cGAS) Deficient Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111450"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1093\/intimm\/dxaf035","article-title":"Less severe tumor growth in mice in which mgmt is conditionally deleted using the LysM-Cre system, and the possible impacts of DNA methylation in tumor-associated macrophages","volume":"37","author":"Phuengmaung","year":"2025","journal-title":"Int. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, D., He, F., Bi, S., Guo, H., Zhang, B., Wu, F., Liang, J., Yang, Y., Tian, Q., and Ju, C. (2016). Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00751"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0165-5728(96)00056-2","article-title":"Induction of immunoreactive interleukin-1 beta and tumor necrosis factor-alpha in the brains of rabies virus infected rats","volume":"68","author":"Marquette","year":"1996","journal-title":"J. Neuroimmunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"de Punder, K., and Pruimboom, L. (2015). Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00223"},{"key":"ref_43","first-page":"e64710","article-title":"Assessment of Gut Barrier Integrity in Mice Using Fluorescein-Isothiocyanate-Labeled Dextran","volume":"189","author":"Gerkins","year":"2022","journal-title":"J. Vis. Exp."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s13238-013-3918-8","article-title":"Role of the blood-brain barrier in rabies virus infection and protection","volume":"4","author":"Wang","year":"2013","journal-title":"Protein Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.1128\/JVI.03149-13","article-title":"Enhancement of blood-brain barrier permeability and reduction of tight junction protein expression are modulated by chemokines\/cytokines induced by rabies virus infection","volume":"88","author":"Chai","year":"2014","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Magne, F., Gotteland, M., Gauthier, L., Zazueta, A., Pesoa, S., Navarrete, P., and Balamurugan, R. (2020). The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?. Nutrients, 12.","DOI":"10.3390\/nu12051474"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nikolic, J., Civas, A., Lama, Z., Lagaudri\u00e8re-Gesbert, C., and Blondel, D. (2016). Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005942"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.chom.2024.07.019","article-title":"Unlocking the mind-gut connection: Impact of human microbiome on cognition","volume":"32","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00109-021-02113-y","article-title":"The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis","volume":"99","author":"Bolourani","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11396","DOI":"10.1128\/JVI.02151-15","article-title":"Downregulation of Toll-Like Receptor 9 Expression by Beta Human Papillomavirus 38 and Implications for Cell Cycle Control","volume":"89","author":"Pacini","year":"2015","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s13365-013-0214-6","article-title":"Mitochondrial dysfunction in rabies virus infection of neurons","volume":"19","author":"Alandijany","year":"2013","journal-title":"J. Neurovirol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/B978-0-12-387040-7.00008-1","article-title":"Role of oxidative stress in rabies virus infection","volume":"79","author":"Jackson","year":"2011","journal-title":"Adv. Virus Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7778","DOI":"10.1073\/pnas.95.13.7778","article-title":"A neuromodulatory role of interleukin-1beta in the hippocampus","volume":"95","author":"Schneider","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1159\/000496467","article-title":"The Arginase Pathway in Neonatal Brain Hypoxia-Ischemia","volume":"40","author":"Krystofova","year":"2018","journal-title":"Dev. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15405","DOI":"10.1128\/JVI.79.24.15405-15416.2005","article-title":"Overexpression of tumor necrosis factor alpha by a recombinant rabies virus attenuates replication in neurons and prevents lethal infection in mice","volume":"79","author":"Faber","year":"2005","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1111\/j.1476-5381.2009.00291.x","article-title":"Arginase: An emerging key player in the mammalian immune system","volume":"158","author":"Munder","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dang, C.P., and Leelahavanichkul, A. (2020). Over-expression of miR-223 induces M2 macrophage through glycolysis alteration and attenuates LPS-induced sepsis mouse model, the cell-based therapy in sepsis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236038"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ismail, F.S., Faustmann, T.J., Faustmann, P.M., and Corvace, F. (2024). Microglia as potential key regulators in viral-induced neuroinflammation. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1426079"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Brandl, S., and Reindl, M. (2023). Blood-Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612699"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cytogfr.2011.02.001","article-title":"Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: Key modulators of innate immune responses to double-stranded RNA viruses","volume":"22","author":"Yu","year":"2011","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s10875-006-9044-0","article-title":"Detection of cellular immunity to rabies antigens in human vaccinees","volume":"26","author":"Moore","year":"2006","journal-title":"J. Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"M\u00e9nager, P., Roux, P., M\u00e9gret, F., Bourgeois, J.P., Le Sourd, A.M., Danckaert, A., Lafage, M., Pr\u00e9haud, C., and Lafon, M. (2009). Toll-like receptor 3 (TLR3) plays a major role in the formation of rabies virus Negri Bodies. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000315"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.cytogfr.2014.05.004","article-title":"RIG-I-like receptors and negative-strand RNA viruses: RLRly bird catches some worms","volume":"25","author":"Weber","year":"2014","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"105321","DOI":"10.1016\/j.micinf.2024.105321","article-title":"Comparative analysis of rabies pathogenic and vaccine strains detection by RIG-I-like receptors","volume":"26","author":"Aouadi","year":"2024","journal-title":"Microbes Infect."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Xie, Y., Chi, Y., Tao, X., Yu, P., Liu, Q., Zhang, M., Yang, N., Liu, S., and Zhu, W. (2024). Rabies Virus Regulates Inflammatory Response in BV-2 Cells through Activation of Myd88 and NF-\u03baB Signaling Pathways via TLR7. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179144"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Embregts, C.W.E., Wentzel, A.S., den Dekker, A.T., van Ijcken, W.F., Stadhouders, R., and GeurtsvanKessel, C.H. (2023). Rabies virus uniquely reprograms the transcriptome of human monocyte-derived macrophages. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1013842"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.2147\/JIR.S384949","article-title":"Vagus Nerve and Underlying Impact on the Gut Microbiota-Brain Axis in Behavior and Neurodegenerative Diseases","volume":"15","author":"Han","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"eadg2252","DOI":"10.1126\/sciadv.adg2252","article-title":"Peripheral nerves directly mediate the transneuronal translocation of silver nanomaterials from the gut to central nervous system","volume":"9","author":"Wang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1590\/S1678-91992006000300008","article-title":"Antibody and cytokine serum levels in patients subjected to anti-rabies prophylaxis with serum-vaccination","volume":"12","author":"Ayres","year":"2006","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"378","DOI":"10.4269\/ajtmh.15-0361","article-title":"Profile of Cytokines and Chemokines Triggered by Wild-Type Strains of Rabies Virus in Mice","volume":"94","author":"Allendorf","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.biopsycho.2009.05.001","article-title":"Transient responses of inflammatory cytokines in acute stress","volume":"82","author":"Yamakawa","year":"2009","journal-title":"Biol. Psychol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Alotiby, A. (2024). Immunology of Stress: A Review Article. J. Clin. Med., 13.","DOI":"10.3390\/jcm13216394"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Panpetch, W., Tumwasorn, S., and Leelahavanichkul, A. (2024). Presence of Pseudomonas aeruginosa in feces exacerbate leaky gut in mice with low dose dextran sulfate solution, impacts of specific bacteria. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0309106"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Rizzatti, G., Lopetuso, L.R., Gibiino, G., Binda, C., and Gasbarrini, A. (2017). Proteobacteria: A Common Factor in Human Diseases. Biomed. Res. Int., 2017.","DOI":"10.1155\/2017\/9351507"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2027853","DOI":"10.1080\/19490976.2022.2027853","article-title":"Bacteroides acidifaciens in the gut plays a protective role against CD95-mediated liver injury","volume":"14","author":"Wang","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/00000658-197711000-00002","article-title":"Bacteroides bacteremia","volume":"186","author":"Lawrence","year":"1977","journal-title":"Ann. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Daca, A., and Jarzembowski, T. (2024). From the Friend to the Foe-Enterococcus faecalis Diverse Impact on the Human Immune System. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042422"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Im, E.J., Lee, H.H., Kim, M., and Kim, M.K. (2023). Evaluation of Enterococcal Probiotic Usage and Review of Potential Health Benefits, Safety, and Risk of Antibiotic-Resistant Strain Emergence. Antibiotics, 12.","DOI":"10.3390\/antibiotics12081327"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Hiengrach, P., Panpetch, W., Chindamporn, A., and Leelahavanichkul, A. (2022). Macrophage depletion alters bacterial gut microbiota partly through fungal overgrowth in feces that worsens cecal ligation and puncture sepsis mice. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-13098-0"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.chom.2015.05.004","article-title":"The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy","volume":"17","author":"Watson","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.5455\/OVJ.2023.v13.i11.1","article-title":"Tracking lethal threat: In-depth review of rabies","volume":"13","author":"Khairullah","year":"2023","journal-title":"Open Vet. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e066587","DOI":"10.1136\/bmjopen-2022-066587","article-title":"Rabies in Southeast Asia: A systematic review of its incidence, risk factors and mortality","volume":"13","author":"Halim","year":"2023","journal-title":"BMJ Open"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e00536","DOI":"10.1016\/j.neurot.2025.e00536","article-title":"Identification and development of cGAS inhibitors and their uses to treat Alzheimer\u2019s disease","volume":"22","author":"Nagiri","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1038\/s41467-023-41892-5","article-title":"Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Li, J., Xiong, M., Liu, J., Zhang, F., Li, M., Zhao, W., and Xu, Y. (2023). Discovery of novel cGAS inhibitors based on natural flavonoids. Bioorg Chem., 140.","DOI":"10.1016\/j.bioorg.2023.106802"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s11940-009-0046-0","article-title":"A modern approach to the treatment of mitochondrial disease","volume":"11","author":"Parikh","year":"2009","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.18632\/aging.205147","article-title":"Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging","volume":"16","author":"Poudel","year":"2024","journal-title":"Aging"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s11940-014-0292-7","article-title":"Treatment of mitochondrial disorders","volume":"16","author":"Avula","year":"2014","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1128\/jvi.55.3.788-795.1985","article-title":"Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice","volume":"55","author":"Lodmell","year":"1985","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101867","DOI":"10.1016\/j.tmaid.2020.101867","article-title":"Factors influencing the immune response after a single-dose 3-visit pre-exposure rabies intradermal vaccination schedule: A retrospective multivariate analysis","volume":"37","author":"Damanet","year":"2020","journal-title":"Travel. Med. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.virusres.2006.05.002","article-title":"Rabies virus-induced apoptosis involves caspase-dependent and caspase-independent pathways","volume":"121","author":"Sarmento","year":"2006","journal-title":"Virus Res."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/11\/1583\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T05:11:21Z","timestamp":1763097081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/11\/1583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":92,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biology14111583"],"URL":"https:\/\/doi.org\/10.3390\/biology14111583","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]}}}