Cytokine最新文献

{"title":"Unveiling the nexus: The tumor microenvironment as a strategic frontier in viral cancers","authors":"Queenie Fernandes ,&nbsp;Oginni Gbenga Folorunsho","doi":"10.1016/j.cyto.2024.156827","DOIUrl":"10.1016/j.cyto.2024.156827","url":null,"abstract":"<div><div>Viral infections are a significant factor in the etiology of various cancers, with the tumor microenvironment (TME) playing a crucial role in disease progression. This review delves into the complex interactions between viruses and the TME, highlighting how these interactions shape the course of viral cancers. We explore the distinct roles of immune cells, including T-cells, B-cells, macrophages, and dendritic cells, within the TME and their influence on cancer progression. The review also examines how viral oncoproteins manipulate the TME to promote immune evasion and tumor survival. Unraveling these mechanisms highlights the emerging paradigm of targeting the TME as a novel approach to cancer treatment. Our analysis provides insights into the dynamic interplay between viruses and the TME, offering a roadmap for innovative treatments that leverage the unique characteristics of viral cancers.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156827"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794146","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":"NK cell-derived exosomes inhibit survival of Mycobacterium tuberculosis by promoting apoptosis in mice.","authors":"Yumei Dai, Xuan Wang, Wenya Du, Ruifeng Chen, Fengqian Ma, Tao Ma, Linzhi Yue, Tongrui Fang, Guofu Wang, Ling Geng, Tao Wang, Lixian Wu","doi":"10.1016/j.cyto.2024.156820","DOIUrl":"10.1016/j.cyto.2024.156820","url":null,"abstract":"<p><strong>Aim: </strong>To investigate anti-Mycobacterium tuberculosis (Mtb) influences exerted by natural killer cell-derived exosomes (NK-exo) on mice and to elucidate underlying immunologic mechanisms.</p><p><strong>Methods: </strong>We established tuberculosis (TB) model in mouse by injecting Mtb H37Ra (1 × 10⁶ colony counting (CFU), i.v.) into tail vein for 14 days. The survival rate of Mtb was assessed through CFU, apoptosis rates were measured utilizing flow cytometry, and inflammation relief was quantified via HE staining. Expressions of apoptosis, inflammation, and pyroptosis-related proteins were quantified by Western blotting and RT-qPCR. ELISA was utilized for detecting inflammatory cytokines production. Intracellular reactive oxygen species (ROS) levels were assessed through DCFH-DA fluorescent probe assay.</p><p><strong>Results: </strong>NK-exo treatment reduced Mtb load in lung and spleen tissues and alleviated inflammation in mice lung tissues. NK-exo intervention increased protein levels of markers associated with apoptosis, PARP and caspase-3/8/9, downregulating the concentrations of pro-inflammatory cytokines, comprising IL-1β, TNF-α, IL-6, along with protein expressions of biomarkers, ASC, NLRP3, GSDMD, associated to inflammation and pyroptosis. NK-exo also elevated ROS levels without affecting lactate dehydrogenase (LDH) release from macrophages.</p><p><strong>Conclusion: </strong>NK-exo exhibits anti-tuberculosis activity in experimental TB mice. The underlying mechanism involve regulating caspase-dependent apoptotic signaling pathway to promote cell apoptosis, as well as modulating NLRP3 signaling pathway to suppress the inflammatory response.</p>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"156820"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754398","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":"Impact of oral flora in tongue coating and saliva on oral cancer risk and the regulatory role of Interleukin-8","authors":"Xiaotang Wang ,&nbsp;Xiaona Song ,&nbsp;Jiping Gao ,&nbsp;Yunhui Ma ,&nbsp;Tian Wang ,&nbsp;Xiaoqi Chang ,&nbsp;Shuxuan Shi ,&nbsp;Yaqi Liu ,&nbsp;Guohua Song","doi":"10.1016/j.cyto.2024.156821","DOIUrl":"10.1016/j.cyto.2024.156821","url":null,"abstract":"<div><h3>Background</h3><div>Oral flora and inflammatory factors play a crucial role in oral cancer, but the relationship between them and oral cancer has not been clearly established.</div></div><div><h3>Methods</h3><div>Oral flora served as exposure factor, oral cancer as outcome factor, and inflammatory factors as mediating factor. Mendelian randomization (MR) analysis was used to analyze the relationship between oral flora and oral cancer, and the potential mediating effect of inflammatory factors was explored through mediation analysis.</div></div><div><h3>Results</h3><div>29 kinds of oral flora in tongue coating and 22 kinds of oral flora in saliva were associated with increased risk of oral cancer. 18 species of oral flora in tongue coating and 25 species in saliva were associated with a reduced risk of oral cancer. Interleukin-8 (IL8) played a mediating role in the relationship between oral flora and oral cancer, and it was associated with an increased risk of oral cancer. <em>Granulicatella</em>, <em>Streptococcus mitis</em>, <em>Saccharimonadaceae</em> and <em>Haemophilus</em> in oral flora caused oral cancer indirectly through IL8. IL8 expression increased in oral cancer, which has good diagnostic value. IL8-related genes in oral cancer are closely associated with immune cell infiltration. What's more, IL8 has potential medicinal properties.</div></div><div><h3>Conclusion</h3><div>Oral flora of tongue coating and saliva is closely related to oral cancer, and IL8 plays a mediating role in the causal relationship between oral flora and oral cancer.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156821"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778711","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 effect of long-term exposure to moderate high altitude on adipokines and insulin sensitivity","authors":"Wenxia Wu ,&nbsp;Guishan Chen ,&nbsp;Xiaoyun Zhang ,&nbsp;Hongshi Wu ,&nbsp;Yu-E Wang ,&nbsp;Xin Li ,&nbsp;Ying Liang ,&nbsp;Dan Liu","doi":"10.1016/j.cyto.2024.156823","DOIUrl":"10.1016/j.cyto.2024.156823","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;High altitude area refers to plateau area with an altitude of 1500 m or above. Short-term (less than 30 days) exposure to high-altitude environments (hypoxia, low temperature, low pressure) might affect the adipokines level and insulin sensitivity. However, whether long-term exposure to moderate high altitude would have an impact on adipokines and insulin sensitivity remains unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study aimed to explore the effect of long-term exposure (12 months) to moderate high altitudes (2900 m) on changes in adipokines level and insulin sensitivity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;48 healthy adults from Guangdong Province (the average altitude less than 50 m) to Nyingchi (an average altitude of 2900 m) were included with follow-up of 12 months. Before entering Nyingchi, baseline anthropometric indicators (height, weight, blood pressure), metabolic indicators: fasting plasma glucose (FPG), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), adipokines: adiponectin and leptin, inflammatory indicators: tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6); hypoxia-inducible factor 1alpha (HIF-1α), oxidative stress indicator: malondialdehyde (MDA), antioxidant indicators: superoxide dismutase (SOD) and glutathione (GSH) were determined. After entering Nyingchi, the above indicators were retested at the 1st, 6th, and 12th month. The control group consist of 47 local residents in Nyingchi. Linear mixed effect model was used to analyze the trend of index changes. Multivariate linear regression analysis was analyzed to explore the influence factors of adiponectin at 12th month.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;After 12 months exposure to high altitude, the body mass index (BMI), systolic blood pressure (SBP) and FPG of subjects decreased from baseline of 23.51 ± 2.68 kg/m&lt;sup&gt;2&lt;/sup&gt;, 123.68 ± 14.94 mmHg and 5.05 ± 0.36 mmol/L to 22.59 ± 2.56 kg/m&lt;sup&gt;2&lt;/sup&gt;, 116.10 ± 14.68 mmHg and 4.65 ± 0.46 mmol/L respectively, HDL-C increased from baseline of 1.30 ± 0.26 mmol/L to 1.37 ± 0.30 mmol/L. HOMA-IR decreased from baseline 1.70 (1.19, 2.22) to 1.25(1.04, 1.78). Adiponectin increased from 3.85(3.05, 4.98) to 4.75(3.33, 5.88) μg/mL, leptin decreased from 1022.10(496.30, 2508.60) to 729.60(308.78, 1670.20) pg/mL. TNFα decreased from 6.81(5.37, 8.49) to 5.50(4.00, 6.74) pg/mL. The level of HIF-1α increased from baseline 1.91 (1.32, 5.09) to 2.94 (1.65, 15.45) pg/mL. SOD increased from 0.20(0.15, 0.24) to 0.25(0.20, 0.28) U/mL. Multivariate linear regression analysis showed that HIF-1α (β = 0.006, 95 %CI, 0.001–0.012, &lt;em&gt;p&lt;/em&gt; = 0.033) and SOD (β = 7.318, 95 %CI, 0.486–14.149, &lt;em&gt;p&lt;/em&gt; = 0.037) was the factors that influenced adiponectin level at 12th month after exposure to high altitude.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Long-term exposure to moderate high-altitude environments could improve insulin sensitivity and adipocy","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156823"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764957","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":"Effects of probiotics on clinical manifestations and inflammatory markers in HTLV-1-associated myelopathy/tropical spastic paraparesis: A triple blind randomized, placebo controlled trial","authors":"Parvaneh Mamaghani Rad ,&nbsp;Zohreh Vahidi ,&nbsp;Mostafa Zemorshidi ,&nbsp;Mohammad Taghi Farzadfard ,&nbsp;Majid Khadem-Rezaiyan ,&nbsp;Reza Boostani ,&nbsp;Mohammad Ali Nahayati ,&nbsp;Houshang Rafatpanah ,&nbsp;Fariba Zemorshidi","doi":"10.1016/j.cyto.2024.156825","DOIUrl":"10.1016/j.cyto.2024.156825","url":null,"abstract":"<div><div>Human T-lymphotropic virus type 1 (HTLV-1), leads to adult T-cell lymphoma/leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of infected individuals. The virus promotes inflammation, a major factor in chronic disease progression. Probiotics' immune modulation and anti-inflammatory effects present a potential therapeutic intervention for HTLV-1-related conditions. This study investigates the impact of probiotics on both clinical manifestations and inflammatory markers in HAM/TSP patients.</div><div>Conducted at the HTLV-1 clinic of Ghaem Hospital (Mashhad, Iran) between 2019 and 2020, this study randomized 40 HAM/TSP patients into two groups: an intervention group receiving 500 mg LactoCare capsules twice daily and a control group receiving placebo capsules of identical appearance for 12 weeks. Baseline and follow-up assessments included muscle strength, spasticity, motor disability, urinary disturbance, and serum levels of IL-10, IL-4, and IFN-γ (measured by ELISA). Post-intervention analysis revealed no significant differences between intervention and control groups in muscle strength, spasticity, and motor disability. However, significant improvement was observed in the intervention group regarding urinary symptoms after 12 weeks of initiation of intervention (<em>P</em> = 0.003). No significant changes were detected in serum levels of IL-10, IL-4, and IFN-γ between the two groups. The probiotics showed positive effects on urinary symptoms in HTLV-1-associated myelopathy/tropical spastic paraparesis patients but did not significantly impact other clinical or paraclinical parameters within the 12-week study period. These findings suggest that probiotics may offer symptomatic relief for some symptoms of HTLV-1-associated myelopathy/tropical spastic paraparesis patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156825"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778707","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":"Unraveling the causal associations between systemic cytokines and six inflammatory skin diseases","authors":"Waner Liu,&nbsp;Xu Zhang,&nbsp;Xiang Chen","doi":"10.1016/j.cyto.2024.156810","DOIUrl":"10.1016/j.cyto.2024.156810","url":null,"abstract":"<div><h3>Background</h3><div>Previous observational studies have reported that systemic cytokines are associated with the risk of inflammatory skin diseases, but their conclusions remain controversial.</div></div><div><h3>Method</h3><div>We conducted a two-sample Mendelian randomization analysis to assess the relationship between systemic cytokines and six inflammatory skin disorders (including alopecia areata (AA), acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis (PS) and vitiligo), based on datasets from EArly Genetics and Lifecourse Epidemiology (EAGLE) eczema consortium, acne GWAS conducted by Maris Teder Laving et al., IEU Open GWAS, and FinnGen database. Inverse-variance weighted (IVW) method was conducted in primary MR analysis, and supplemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO.</div></div><div><h3>Results</h3><div>By integrating the findings from both primary and sensitivity analyses, we identified ten systemic cytokines linked to the risk of six skin diseases using the IVW method. Briefly, four cytokines increased the risk of corresponding skin diseases: β-nerve growth factor (β-NGF) to AA (p = 0.005) and HS (p = 0.001), interleukin-8 (p = 0.014) to acne; interleukin-5 (p = 0.042) to AD; interleukin-13 (p = 0.049) to PS. In the meantime, seven cytokines could have protective effect on specific skin diseases: interleukin-9 (p = 0.040) and interleukin-2 receptor subunit alpha (IL-2ra) (p = 0.020) on AA; macrophage inflammatory protein (MIP)-1β (p = 0.020) on acne; monokine induced by IFN-γ (p = 0.006) on AD; interleukin-16 (p = 0.038), MIP-1β (p = 0.017) and IL-2ra (p = 0.020) on PS.</div></div><div><h3>Conclusions</h3><div>This study reveals 13 causal associations between systemic cytokines and 6 skin diseases, offering new perspectives on the prevention and management of widespread inflammatory skin disorders.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156810"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778714","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":"Anti-CD8/IL-15 (N72D)/sushi fusion protein: A promising strategy for improvement of cancer immunotherapy","authors":"Nafiseh Maghsoodi ,&nbsp;Mohammadrasul Zareinejad ,&nbsp;Abbas Ghaderi ,&nbsp;Elham Mahmoudi Maymand ,&nbsp;Cambyz Irajie ,&nbsp;Amin Ramezani","doi":"10.1016/j.cyto.2024.156822","DOIUrl":"10.1016/j.cyto.2024.156822","url":null,"abstract":"<div><h3>Background</h3><div>To overcome the limitations of IL-15 and to improve the efficacy of IL-15 in immunotherapy, several strategies have been introduced.</div></div><div><h3>Objective</h3><div>The objective of this study was to generate and evaluate a novel anti-CD8/IL-15 (N72D)/Sushi fusion protein with the potential to target CD8⁺ T cells and enhance functionality of CD8⁺ T cells against tumor cells.</div></div><div><h3>Methods</h3><div>In this connection, a novel fusokine that contains IL-15(N72D), a Sushi domain, and anti-CD8 single-chain fragment variable (scFv) was designed. The size accuracy and binding potency of the isolated protein were assessed using western blotting and indirect surface staining. Following purification, the potential function of the anti-CD8/IL-15(N72D)/Sushi fusion protein in the induction of proliferation and cytotoxicity of CD8⁺ T cells was evaluated.</div></div><div><h3>Results</h3><div>In-silico analysis revealed that fusokine is structurally stable, correctly folded and can interact with the CD8 co-receptor. Both fusokine and IL-15(N72D)/Sushi were produced in CHO-S cell line with a final concentration of 18.43 mg/l and 12.64 mg/l respectively. Fusokine bound to 97.6 % of CD8⁺ T cells and significantly induced T cell proliferation and cytotoxic potential in peripheral blood mononuclear cells (PBMCs) in a time dependent manner. Compared to both the control and the IL-15 (N72D)/sushi treated groups, fusokine showed superior potential in CD8⁺ T cell functionality.</div></div><div><h3>Conclusion</h3><div>Anti-CD8/IL-15(N72D)/Sushi has the ability to effectively target CD8⁺ T cells, promote lymphocyte proliferation and induce cytotoxicity against tumor cells. Due to its promising properties, it could be considered as a new potential immunotherapy approach.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156822"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778704","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":"Messages in CD40L are encrypted for residue-specific functions","authors":"Akshata Bammigatti ,&nbsp;Soumya Kanti Ghosh ,&nbsp;Syamdas Bandyopadhyay ,&nbsp;Bhaskar Saha","doi":"10.1016/j.cyto.2024.156824","DOIUrl":"10.1016/j.cyto.2024.156824","url":null,"abstract":"<div><div>CD40-CD40-ligand (CD40L) interaction plays crucial immunoregulatory roles, as CD40 signals through different signaling intermediates to convert the messages from CD40L to effector functions. Being a TNFα receptor family member, CD40 binds TNFα receptor-associated factors, assembles signalosome complexes and decrypts the messages from CD40L through different signaling modules to result in residue-specific effector functions. The evidence for such a residue-specific message encryption first came from the CD40L mutations resulting in X-linked hyper-IgM syndrome, as the extent of effects varied with the residue mutated. The structural studies on the CD40-CD40L interaction implied differential involvement of the interacting residues on CD40L in influencing the effector functions. Three lines of evidence indicate the previously implied residue-specific message encryption in CD40L: screening of a dodecameric peptide library for CD40 binders identified two peptides with different sequences resulting in counteractive effector functions in macrophages; a series of CD40L mutants identified that the mutations in these residues selectively affected CD40 signaling and macrophage effector functions; and, a panel of 40-mer peptides, representing the CD40-interacting domain of mouse CD40L, with single substitutions resulted in altered CD40 signaling through various signaling intermediates and effector functions in mouse macrophages. We therefore construct the first-ever message encryption-decryption in a biological receptor-ligand system wherein the CD40L residues that interact with CD40 residues have encrypted messages, which are decoded by CD40 signaling to result in residue-specific effector functions. This review presents a novel perspective of receptor-ligand interaction as a system of message transmission, message decoding by signaling, and its transcription to various read-outs. [250 words].</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156824"},"PeriodicalIF":3.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745199","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":"Inverse correlation between Leishmania-induced TLR1/2 and TGF-β differentially regulates parasite persistence in bone marrow during the chronic phase of infection.","authors":"Kamalika Roy,&nbsp;Sanhita Ghosh,&nbsp;Suman Karmakar,&nbsp;Pritam Mandal,&nbsp;Aabid Hussain ,&nbsp;Aritri Dutta ,&nbsp;Chiranjib Pal","doi":"10.1016/j.cyto.2024.156811","DOIUrl":"10.1016/j.cyto.2024.156811","url":null,"abstract":"<div><div>Host-tissue preference is a critical aspect of parasitic infections and is directly correlated with species diversity. Even the same species, <em>Leishmania donovani</em>, infects the host's bone marrow, spleen, and liver differentially. The tissue-specific persistence of <em>Leishmania</em> results from host-pathogen immune conflicts and arguments. The protective pro-host or destructive pro-parasitic role of TLRs during <em>L</em>. <em>donovani</em> infection has been well established, but what entirely missing is the influence of TLRs on tissue-specific parasite persistence. We observed that the parasites induced differential expression of TLR1/2 in the bone marrow but not in the spleen. Interestingly, the rate of <em>Leishmania</em> infection was found to be positively correlated with TLR1/2-mediated upregulation of myelopoietic cytokines, M-CSF, GM-CSF, IL-6, and IL-3, leading to the expansion of Ly6C^hiCCR2⁺ monocytes, however, negatively correlated with the expression of the disease hallmark cytokines, TNF-α, TGF-β, and IL-10, along the course of infection in the bone marrow. <em>Leishmania</em> induced the activation of bone marrow-specific TLR1/2 to promote Ly6C^hiCCR2⁺ monocytes for its safe shelter vis-à-vis infection establishment. Consequently, the established infection initiated the release of TNF-α, TGF-β, and IL-10 in the bone marrow. Post-infection time-kinetic study affirmed that TGF-β had a significant negative influence on the expression of TLR1/2 heterodimer in the bone marrow niche. To the best of our knowledge, this is the first report to show that the inverse correlation of TLR1/2 - TGF-β can be instrumental in tissue-specific parasite persistence during <em>Leishmania</em> infection.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156811"},"PeriodicalIF":3.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720712","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":"Higher levels of IL-6 and IL-10 cytokines in visceral leishmaniasis-HIV co-infected patients from Brazilian high endemic area","authors":"Larissa Di Leo Nogueira Costa ,&nbsp;Cristiane Michele Sampaio Cutrim ,&nbsp;Gustavo de Almeida Santos ,&nbsp;Uiara Regina Silva de Lima ,&nbsp;Thayná Matos de Sousa ,&nbsp;Johnny Ramos do Nascimento ,&nbsp;Lucilene Amorim Silva ,&nbsp;Hivana Patricia Melo Barbosa Dall'Agnol ,&nbsp;Leonardo Teixeira Dall'Agnol ,&nbsp;Vandilson Pinheiro Rodrigues ,&nbsp;Conceição de Maria Pedrozo Silva de Azevedo ,&nbsp;Mayara Ingrid Sousa Lima","doi":"10.1016/j.cyto.2024.156812","DOIUrl":"10.1016/j.cyto.2024.156812","url":null,"abstract":"<div><div>Visceral Leishmaniasis (VL) is an endemic disease in Latin America, and the clinical outcome worsens when a patient has HIV co-infection. In these patients, the immune response is complex and cytokines profile variable. We evaluate Th1/Th2/Th17 cytokine profile in VL/HIV patients from Brazilian high endemic area. In this cross-sectional study, the serological cytokines production was compared with clinical and epidemiological traits of the VL/HIV, VL and HIV patients. VL/HIV patients are predominantly male (89.2 %) with relapses in 35.5 % of the cases. There is higher serum levels of IL-6 (<em>p</em> = 0.006) and IL-10 (<em>p</em> &lt; 0.001) in VL/HIV patients. Furthermore, there is a moderate or strong positive correlation in the serum levels of IL-6 and TNF-α (Rho = 0.635, <em>p</em> &lt; 0.001), IL-10 and IFN-γ (Rho = 0.523, p &lt; 0.001), IL-6 and IL-10 (Rho = 0.506, p &lt; 0.001), IL-2 and IL-4 (Rho = 0.506, p &lt; 0.001). Then, VL/HIV patients who died during VL treatment (<em>p</em> = 0.033), patients with oedema (<em>p</em> = 0.011), and patients with jaundice (<em>p</em> = 0.019) had statistically high levels of IL-6. In conclusion, VL/HIV patients have production or reduction of specific cytokines, highlights IL-6 and IL-10.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"185 ","pages":"Article 156812"},"PeriodicalIF":3.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720709","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}