Journal of Leukocyte Biology最新文献

{"title":"Eosinophils as modulators of host defense during parasitic, fungal, bacterial, and viral infections.","authors":"Pedro H Gazzinelli-Guimaraes, Shelby M Jones, David Voehringer, Katrin D Mayer-Barber, Amali E Samarasinghe","doi":"10.1093/jleuko/qiae173","DOIUrl":"10.1093/jleuko/qiae173","url":null,"abstract":"<p><p>Eosinophils, traditionally associated as central innate effector cells with type 2 immunity during allergic and helminth parasitic diseases, have recently been revealed to have important roles in tissue homeostasis as well as host defense in a broader variety of infectious diseases. In a dedicated session at the 2023 biennial conference of the International Eosinophil Society titled \"Eosinophils in Host Defense,\" the multifaceted roles eosinophils play against diverse pathogens, ranging from parasites to fungi, bacteria, and viruses, were presented. In this review, the session speakers offer a comprehensive summary of recent discoveries across pathogen classes, positioning eosinophils as pivotal leukocytes in both host defense and pathology. By unraveling the intricacies of eosinophil engagement in host resistance, this exploration may provide valuable insights not only to understand specific underpinnings of eosinophil functions related to each class of pathogens but also to develop novel therapeutics effective against a broad spectrum of infectious diseases.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1301-1323"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated viral and immune monitoring in a prospective COVID-19 cohort from India.","authors":"Sachee Agrawal, Nandini Kasarpalkar, Sayantani Ghosh, Gaurav Paradkar, Vaibhav Daund, Shilpa Bhowmick, Vidushi Chitalia, Priyanka Rao, Ashwini Sankpal, Varsha Kalsurkar, Karan Shah, Sameen Khan, Ashwini Patil, Dhanashree Jagtap, Omkar Khandkar, Mala Kaneria, Smita D Mahale, Geetanjali Sachdeva, Vikrant M Bhor, Jayanthi Shastri, Vainav Patel","doi":"10.1093/jleuko/qiae187","DOIUrl":"10.1093/jleuko/qiae187","url":null,"abstract":"<p><p>In this study, we report on longitudinal kinetics of cellular immune subsets following SARS-CoV-2 infection in a cohort of hospitalized individuals and evaluate the interplay of these profiles with infecting viral variants, humoral immunity including neutralizing responses, vaccination history, and clinical outcomes. A cohort of 121 SARS-CoV-2-infected individuals exhibiting varying disease states were prospectively evaluated for lymphopenic profiles, antiviral humoral responses and infecting viral variants for a period of up to 90 d spanning the period of February 2021 to January 2022 (second and third waves of infection). A total of 51 participants received at least 1 vaccine dose of indigenous vaccines (Covishield or Covaxin) prior to recruitment. When stratified in terms of mortality, B and natural killer cells, in contrast to the T cell compartment, did not recover from nadir levels in nonsurvivors who were largely unvaccinated. No discriminatory signature was identified for nonsurvivors in terms of anti-nucleocapsid or anti-S1-RBD IgG chemiluminescent immunoassay profiles including GenScript S1-RBD assays. Evaluation of sVCAM and sMAdCAM revealed opposing dynamics that correlated with disease severity and convalescence respectively. Viral variant analysis revealed Delta and Omicron variants to comprise the majority of the infections, which reflected national transmission kinetics during the period of recruitment. Our results demonstrate the importance of monitoring circulating biomarkers for convalescence as well as mortality in COVID-19 progression. Delta variants of SARS-CoV-2 clearly demonstrated increased pathogenicity and warrants sustained viral surveillance for re-emergence of these strains. Our findings with respect to vaccination advocate for continued vaccine development and administration of COVID-19 vaccines.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1568-1577"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vanin-2 is expressed in peripheral blood T cells and upregulated in patients with systemic lupus erythematosus.","authors":"Chen Liu, Xiayidan Alimu, Xingyue Zeng, Ayibaota Bahabayi, Yiming Gao, Yuzhe Hu, Yang Chen, Junjie Zhao, Xinran Lian, Mohan Zheng, Tianci Liu, Pingzhang Wang","doi":"10.1093/jleuko/qiae145","DOIUrl":"10.1093/jleuko/qiae145","url":null,"abstract":"<p><p>Members of the vanin gene family include VNN1, VNN2, and VNN3 in humans. Although the functions of vanins have been widely examined in myeloid cells, their expression and functions have not been clarified in T lymphocytes. This study aimed to elucidate the significance of Vanin-2 (VNN2) on human peripheral blood T lymphocytes and study its expression in systemic lupus erythematosus (SLE). The differential expression of Vanins was analyzed by bioinformatics. VNN2 expressions in peripheral blood T-cell subsets were analyzed by single-cell RNA sequencing data and flow cytometry. Changes of VNN2 expression before and after T-cell activation were further clarified by western blot. The function of VNN2+ cells was studied by granzyme B (GZMB) and perforin detection. Changes in VNN2+ proportions in T-cell subsets of patients with SLE were further analyzed. In the present study, only VNN2 among vanins showed distinguishable expression in T cells. VNN2+ percentages were higher in CD8+ T cells those in CD4+ T cells. VNN2+ T cells were with a higher memory T-cell composition. VNN2 expression was significantly increased after T-cell stimulation. VNN2+ T cells had higher levels of GZMB and perforin secretion than VNN2- T cells. Clinically, VNN2+ percentages in T cells of patients with SLE were upregulated. Together, these data suggested that VNN2 is expressed in peripheral blood T cells characterized more GZMB and perforin secretion, and increased VNN2+ T cells in patients with SLE could reflect altered T-cell functions in vivo.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1469-1478"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neonatal liver hosts a spontaneously occurring neutrophil population, exhibiting distinct spatial and functional characteristics from adults.","authors":"Wanderson Ferreira da Silva Júnior, Maria Alice de Freitas Lopes, Maísa Mota Antunes, Karen Marques de Oliveira Costa, Ariane Barros Diniz, Brenda Naemi Lanza Nakagaki, Camila Dutra Moreira de Miranda, Hortência Maciel de Castro Oliveira, Alesandra Corte Reis, Stephania Libreros, Cristina Maria Pinto de Paula, Rafael Machado Rezende, Gustavo Batista Menezes","doi":"10.1093/jleuko/qiae082","DOIUrl":"10.1093/jleuko/qiae082","url":null,"abstract":"<p><p>The elusive nature of the liver immune system in newborns remains an important challenge, casting a shadow over our understanding of how to effectively treat and prevent diseases in children. Therefore, deeper exploration into the intricacies of neonatal immunology might be crucial for improved pediatric healthcare. Using liver intravital microscopy, we unveiled a significant population of granulocytes in the hepatic parenchyma of fetuses and newborns. Utilizing high-dimensional immunophenotyping, we showed dynamic alterations predominantly in granulocytes during neonatal development. Liver intravital microscopy from birth through adulthood captures real-time dynamics, showing a substantial presence of Ly6G+ cells that persisted significantly up to 2 wk of age. Using time-of flight mass cytometry, we characterized neonatal Ly6G+ cells as neutrophils, confirmed by morphology and immunohistochemistry. Surprisingly, the embryonic liver hosts a distinct population of neutrophils established as early as the second gestational week, challenging conventional notions about their origin. Additionally, we observed that embryonic neutrophils occupy preferentially the extravascular space, indicating their early establishment within the liver. Hepatic neutrophils in embryos and neonates form unique cell clusters, persisting during the initial days of life, while reduced migratory capabilities in neonates are observed, potentially compensating with increased reactive oxygen species release in response to stimuli. Finally, in vivo imaging of acute neutrophil behavior in a newborn mouse, subjected to focal liver necrosis, unveils that neonatal neutrophils exhibit a reduced migratory response. The study provides unprecedented insights into the intricate interplay of neutrophils within the liver, shedding light on their functional and dynamic characteristics during development.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1352-1363"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E-cigarette vapor extract alters human eosinophil gene expression in an effect mediated by propylene glycol, glycerin, and nicotine.","authors":"Nicholas T Hogan, Francisco Emmanuel Castaneda-Castro, Ashmitaa Logandha Ramamoorthy Premlal, Howard Brickner, Monalisa Mondal, Sara Herrera-De La Mata, Pandurangan Vijayanand, Laura E Crotty Alexander, Gregory Seumois, Praveen Akuthota","doi":"10.1093/jleuko/qiae176","DOIUrl":"10.1093/jleuko/qiae176","url":null,"abstract":"<p><p>E-cigarette use has become widespread, and its effects on airway inflammation and disease are not fully delineated. E-cigarette vapor extract (EVE) profoundly affects neutrophil function. We hypothesized that EVE also alters eosinophil function and thus could impact allergic airway disease. We employed RNA sequencing to measure the ex vivo effect of EVE components on human eosinophil transcription. Blood eosinophils from 9 nonvaping subjects without asthma were isolated by negative selection. Cells were incubated for 48 h with EVE consisting of glycerin, propylene glycol, and nicotine (EVE+), EVE without nicotine (\"EVE-\"), air-exposed media termed extract buffer (EB), or untreated media. Bulk RNA sequencing was performed. Transcriptomic analysis revealed that the EB, EVE-, and EVE+ conditions showed highly variable gene expression with respect to no treatment and each other. Differential gene expression analysis comparing a combination of EVE+, EVE-, and EB revealed 3,030 differentially expressed genes (DEGs) with an adjusted P value <0.05 and log2 fold change >0.5 or <0.5. There were 645 DEGs between EB and EVE-, 1,713 between EB and EVE+, and 404 between EVE- and EVE+. Gene set enrichment analysis demonstrated that DEGs between both EVE+ and EVE- and the EB control were positively enriched for heme metabolism and apoptosis and negatively enriched tumor necrosis factor α signaling, interferon γ signaling, and inflammatory response. Thus, EVE significantly alters eosinophil metabolic and inflammatory pathways, mediated by propylene glycol and glycerin, with both enhancing and unique effects of nicotine. This study motivates further research into the pathogenic effects of vaping on airway eosinophils and allergic airways disease.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1420-1431"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic cell-specific deletion of PKCδ in offspring of allergic mothers prevents the predisposition for development of allergic lung inflammation in offspring.","authors":"Jacquelyn D Lajiness, Jeffrey C Bloodworth, Ross L Blankenship, Allison E Kosins, Joan M Cook-Mills","doi":"10.1093/jleuko/qiae207","DOIUrl":"10.1093/jleuko/qiae207","url":null,"abstract":"<p><p>In humans and in mice, maternal allergy predisposes offspring to development of allergy. In murine models, increased levels of maternal β-glucosylceramides are both necessary and sufficient for the development of allergic predisposition in offspring. Furthermore, increased numbers of CD11b+ dendritic cell subsets in the offspring of allergic mothers are associated with allergic predisposition. In vitro, β-glucosylceramides increase CD11b+ dendritic cell subset numbers through increased PKCδ signaling, but it is not known if enhanced PKCδ signaling in dendritic cells is required in vivo. We demonstrate that dendritic cell-specific deletion of PKCδ prevents the β-glucosylceramide-induced increase in CD11b+ dendritic cell subset numbers both in vitro as well as in vivo in the fetal liver of offspring of mothers injected with β-glucosylceramides. Furthermore, dendritic cell-specific deletion of PKCδ in offspring prevents the maternal allergy-induced increase in CD11b+ dendritic cell subsets and decreases allergen-induced interleukin-5 and eosinophilia in lungs of offspring. However, loss of PKCδ in dendritic cells did not prevent development of allergen-specific IgE. Our study provides mechanistic insight into the function of PKCδ in the origins of allergic disease beginning in utero as well as in the development of postnatal allergic lung inflammation.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1432-1445"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential changes in mast cells with food reintroduction in children with eosinophilic esophagitis.","authors":"Andrew Ebanks, Ming-Yu Wang, Natalie Hoffmann, Barry K Wershil, Joshua B Wechsler","doi":"10.1093/jleuko/qiae174","DOIUrl":"10.1093/jleuko/qiae174","url":null,"abstract":"<p><p>Intraepithelial mast cells (MCs) are increased in eosinophilic esophagitis (EoE) and reduced with elimination of dietary antigens. Single food reintroduction can identify triggers of eosinophilia; however, the extent to which specific foods trigger intraepithelial mastocytosis remains unknown. We hypothesized that specific foods drive different degrees of MC inflammation. We previously reported a prospective pediatric EoE cohort treated with a 4-food elimination diet (4FED) with removal of soy, egg, wheat, and milk. We retrieved unstained slides in which baseline, 4FED, and post-4FED diet reintroduction time points were available. Slides were stained with tryptase, and intraepithelial MCs were counted. Comparisons were made by stratifying patients by eosinophilia, basal cell hyperplasia (BCH), endoscopic abnormalities, and symptoms. Pearson correlation was assessed for MCs with eosinophilic, endoscopic, and BCH severity; symptoms; and a novel mucosal activity score combining endoscopic and histologic structural severity. Slides were available from 37 patients with at least 1 food reintroduced. MCs were significantly reduced with 4FED. Wheat led to increased intraepithelial MCs in the upper esophagus and with food-induced eosinophilia, while milk led to significantly increased MCs in the upper and lower esophagus and was significantly associated with patients with food-triggered eosinophilia, endoscopic abnormalities, BCH, and symptoms. MCs best correlated with the mucosal activity score during milk reintroduction. In children with EoE, MCs are reduced with 4FED. During milk reintroduction, significant increases in MCs were observed with all metrics of inflammation along with moderate correlation with structural mucosal activity that was not seen with other foods. This suggests that milk exerts unique effects either directly or indirectly on MCs in the esophagus in EoE patients.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1412-1419"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accumulation of lipid droplets induced by Listeria monocytogenes in macrophages: implications for survival and evasion of innate immunity.","authors":"Filipe S Pereira-Dutra, Ellen K Souza, Tamyris S Souza, Taynná C Goltara-Gomes, Felipe Ferraro-Moreira, Lohanna Palhinha, Tamires Cunha-Fernandes, Matheus A Rajão, Adriana R Silva, Patrícia T Bozza","doi":"10.1093/jleuko/qiae115","DOIUrl":"10.1093/jleuko/qiae115","url":null,"abstract":"<p><p>Listeriosis, caused by Listeria monocytogenes (L.m.), poses a significant public health concern as one of the most severe foodborne diseases. The pathogenesis of L.m. involves critical steps such as phagosome rupture and escape upon internalization. Throughout infection, L.m. influences various host processes, including lipid metabolism pathways, yet the role of lipid droplets (LDs) remains unclear. Here, we reported a rapid, time-dependent increase in LD formation in macrophages induced by L.m. LD biogenesis was found to be dependent on L.m. viability and virulence genes, particularly on the activity of the pore-forming protein listeriolysin O (LLO). The prevention of LD formation by inhibiting diacylglycerol O-acyltransferase 1 (DGAT1) and cytosolic phospholipase A2 (cPLA2) significantly reduced intracellular bacterial survival, impaired prostaglandin E2 synthesis, and decreased interleukin-10 production. Additionally, inhibiting LD formation led to increased levels of tumor necrosis factor α and interferon β. Collectively, our data suggest a role for LDs in promoting L.m. cell survival and evasion within macrophages.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1364-1371"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recruitment of neutrophils in glomeruli in early mouse sepsis is associated with E-selectin expression and activation of endothelial nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways.","authors":"Zhendong Wang, Erna-Zulaikha Dayang, Peter J Zwiers, Martha L Hernandez Garcia, Matthijs Luxen, Matijs van Meurs, Jan A A M Kamps, Jill Moser, Grietje Molema","doi":"10.1093/jleuko/qiae146","DOIUrl":"10.1093/jleuko/qiae146","url":null,"abstract":"<p><p>Sepsis is a dysregulated systemic inflammatory response to an infection, which can lead to multiple organ dysfunction syndrome that includes the kidney. Leukocyte recruitment is an important process of the host immune defense in response to sepsis. Endothelial cells (EC) actively regulate leukocyte recruitment by expressing adhesion molecules following the activation of dedicated intracellular signal transduction pathways. Previous studies reported that the expression of adhesion molecules was associated with the activation of endothelial nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 and mitogen-activated protein kinase (MAPK) c-Jun pathways in vitro in response to conditions that mimic processes that occur in inflammation. This study aimed to investigate the spatiotemporal patterns of leukocyte recruitment, expression of adhesion molecules, and endothelial nuclear p65 and c-Jun localization in renal microvascular beds of septic mice. Here, we used a cecal ligation and puncture (CLP) sepsis mouse model and RT-qPCR and immunohistochemical staining. We showed that neutrophils, macrophages, and T lymphocytes were all present in the kidney, yet only neutrophils accumulated in a spatiotemporally discernible pattern, mainly in glomeruli at 4 h after CLP sepsis initiation. E-selectin, not vascular cell adhesion molecule-1 (VCAM-1), was expressed in glomeruli at the same time point. In a subset of mice at 72 h after CLP sepsis started, VCAM-1 expression was prominent in glomerular EC, which was not related to changes in mmu-microRNA(miR)-126a-3p levels, a short noncoding microRNA previously shown to inhibit the translation of VCAM-1 mRNA into protein. Nuclear localization of p65 and c-Jun occurred in EC of all microvascular segments at 4 and 7 h after CLP sepsis initiation. In summary, sepsis-induced recruitment of neutrophils, E-selectin expression, and NF-κB p65 and MAPK c-Jun pathway activation coincided in glomeruli at the early stage of the disease. In the other microvascular beds, sepsis led to NF-κB p65 and MAPK c-Jun pathway activation with limited expression of E-selectin and no association with VCAM-1 expression or leukocyte recruitment.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1479-1497"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the effect of X-ray or proton brain irradiation on systemic inflammation and leukocyte subpopulation interplay in rodents.","authors":"Thao-Nguyen Pham, Julie Coupey, Marc Rousseau, Juliette Thariat, Samuel Valable","doi":"10.1093/jleuko/qiae156","DOIUrl":"10.1093/jleuko/qiae156","url":null,"abstract":"<p><p>The absolute lymphocyte count (ALC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR) offer convenient means to assess systemic inflammation post-cancer treatment, which influences treatment outcomes. Understanding these biomarker variations and leukocyte subpopulation interplay is crucial for optimizing radiotherapy. Herein, leukocyte subpopulations (T-CD4+, T-CD8+, B cells, NK cells, neutrophils, monocytes) during and after brain irradiation (using X-rays or protons) in tumor-free mice were used to compute ALC, LMR, and NLR, on which radiation parameter influence was assessed by principal component analysis (PCA). NLR kinetics was further examined using modeling. Leukocyte subpopulation interplays and their response to radiation parameters were examined using PCA and correlation analysis. Under X-rays, ALC and LMR decreased, with ALC recovered to baseline after irradiation, but not LMR. Both X-rays and protons increased the NLR during irradiation, recovering in protons but not X-rays. Both irradiation volume and dose rate had a pronounced effect on the NLR. Leukocyte subpopulation interplay was observed under X-rays and protons, normalizing in the proton group by day 28. Lymphopenia was observed in all lymphocyte subpopulations under X-ray irradiation but not protons. The recovery patterns varied among the subpopulations. Neutrophil counts increased during irradiation, with the recovery of protons, but not X-rays, by day 28. Interplays between NK cells and myeloid subpopulations were evident under X-rays but not protons. Importantly, no interplay was detected between myeloid cells and T/B cells, indicating that LMR and NLR variations were primarily due to independent responses to brain irradiation. A tumor-free experimental mouse model was used to study the effects of brain radiotherapy on systemic immunity. When administering fractionated irradiation with a total dose of 20 Gy using a vertical beam to either the whole brain or hemi-brain, proton irradiation had fewer adverse impacts on the immune system compared to X-rays in tumor-free rodents.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":"1530-1543"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}