ImmunoHorizons最新文献

{"title":"Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.","authors":"Trang Anh Thi Tran, Yasunori Iwata, Linh Thuy Hoang, Shinji Kitajima, Shiori Yoneda-Nakagawa, Megumi Oshima, Norihiko Sakai, Tadashi Toyama, Yuta Yamamura, Hiroka Yamazaki, Akinori Hara, Miho Shimizu, Keisuke Sako, Taichiro Minami, Takahiro Yuasa, Keisuke Horikoshi, Daiki Hayashi, Sho Kajikawa, Takashi Wada","doi":"10.4049/immunohorizons.2300069","DOIUrl":"10.4049/immunohorizons.2300069","url":null,"abstract":"<p><p>Despite treatment advances, acute kidney injury (AKI)-related mortality rates are still high in hospitalized adults, often due to sepsis. Sepsis and AKI could synergistically worsen the outcomes of critically ill patients. TLR4 signaling and mitochondrial antiviral signaling protein (MAVS) signaling are innate immune responses essential in kidney diseases, but their involvement in sepsis-associated AKI (SA-AKI) remains unclear. We studied the role of MAVS in kidney injury related to the TLR4 signaling pathway using a murine LPS-induced AKI model in wild-type and MAVS-knockout mice. We confirmed the importance of M1 macrophage in SA-AKI through in vivo assessment of inflammatory responses. The TLR4 signaling pathway was upregulated in activated bone marrow-derived macrophages, in which MAVS helped maintain the LPS-suppressed TLR4 mRNA level. MAVS regulated redox homeostasis via NADPH oxidase Nox2 and mitochondrial reverse electron transport in macrophages to alleviate the TLR4 signaling response to LPS. Hypoxia-inducible factor 1α (HIF-1α) and AP-1 were key regulators of TLR4 transcription and connected MAVS-dependent reactive oxygen species signaling with the TLR4 pathway. Inhibition of succinate dehydrogenase could partly reduce inflammation in LPS-treated bone marrow-derived macrophages without MAVS. These findings highlight the renoprotective role of MAVS in LPS-induced AKI by regulating reactive oxygen species generation-related genes and maintaining redox balance. Controlling redox homeostasis through MAVS signaling may be a promising therapy for SA-AKI.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089747","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}

{"title":"Oxidized Low-Density Lipoprotein Accumulation in Macrophages Impairs Lipopolysaccharide-Induced Activation of AKT2, ATP Citrate Lyase, Acetyl-Coenzyme A Production, and Inflammatory Gene H3K27 Acetylation.","authors":"Kenneth K Y Ting, Pei Yu, Mudia Iyayi, Riley Dow, Sharon J Hyduk, Eric Floro, Hisham Ibrahim, Saraf Karim, Chanele K Polenz, Daniel A Winer, Minna Woo, Jonathan Rocheleau, Jenny Jongstra-Bilen, Myron I Cybulsky","doi":"10.4049/immunohorizons.2300101","DOIUrl":"10.4049/immunohorizons.2300101","url":null,"abstract":"<p><p>The accumulation of lipid and the formation of macrophage foam cells is a hallmark of atherosclerosis, a chronic inflammatory disease. To better understand the role of macrophage lipid accumulation in inflammation during atherogenesis, we studied early molecular events that follow the accumulation of oxidized low-density lipoprotein (oxLDL) in cultured mouse macrophages. We previously showed that oxLDL accumulation downregulates the inflammatory response in conjunction with downregulation of late-phase glycolysis. In this study, we show that within hours after LPS stimulation, macrophages with accumulated oxLDL maintain early-phase glycolysis but selectively downregulate activation of AKT2, one of three AKT isoforms. The inhibition of AKT2 activation reduced LPS-induced ATP citrate lyase activation, acetyl-CoA production, and acetylation of histone 3 lysine 27 (H3K27ac) in certain inflammatory gene promoters. In contrast to oxLDL, multiple early LPS-induced signaling pathways were inhibited in macrophages with accumulated cholesterol, including TBK1, AKT1, AKT2, MAPK, and NF-κB, and early-phase glycolysis. The selective inhibition of LPS-induced AKT2 activation was dependent on the generation of mitochondrial oxygen radicals during the accumulation of oxLDL in macrophages prior to LPS stimulation. This is consistent with increased oxidative phosphorylation, fatty acid synthesis, and oxidation pathways found by comparative transcriptomic analyses of oxLDL-loaded versus control macrophages. Our study shows a functional connection between oxLDL accumulation, inactivation of AKT2, and the inhibition of certain inflammatory genes through epigenetic changes that occur soon after LPS stimulation, independent of early-phase glycolysis.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"57-73"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405670","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}

{"title":"Chimeric Antigen Cytotoxic Receptors for In Vivo Engineering of Tumor-Targeting NK Cells.","authors":"Neha Diwanji, Daniel Getts, Yuxiao Wang","doi":"10.4049/immunohorizons.2300099","DOIUrl":"10.4049/immunohorizons.2300099","url":null,"abstract":"<p><p>Chimeric Ag receptor (CAR) NK cells are challenging to manufacture and fail to achieve consistent tumor infiltration and sustained cytolytic function in the tumor microenvironment. In vivo engineering of NK cells using mRNA-based CAR delivery may overcome these issues. In this study, we developed an in vivo programming method by designing CARs that leverage the biology of NK cell receptors for cell type-specific expression and function. These CARs were engineered by fusion of a tumor recognition domain with the natural cytotoxic receptor family including NKp30, NKp44, and NKp46. Our results demonstrated that these natural cytotoxic receptor-based CARs can engage endogenous signaling adaptors to effectively activate human NK cells for tumor lysis and cytokine production. Specifically, we discovered that stable expression of an NKp44-based CAR was contingent on the presence of the immune cell-specific signaling adaptor DAP12. This innovative strategy facilitates direct in situ programming of NK cells, enhancing safety and minimizing off-target effects in nontargeted, healthy tissues.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"97-105"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492263","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}

{"title":"TLR4 Ligands in Typhoid Vi Polysaccharide Subunit Vaccines Contribute to Immunogenicity.","authors":"Kishore R Alugupalli","doi":"10.4049/immunohorizons.2300085","DOIUrl":"10.4049/immunohorizons.2300085","url":null,"abstract":"<p><p>Activation of B cells and T cells requires the engagement of costimulatory signaling pathways in addition to Ag receptor signaling for efficient immune responses. None of the typhoid Vi polysaccharide (ViPS) subunit vaccines contains adjuvants that could activate costimulatory signaling pathways, yet these vaccines are very immunogenic. I hypothesized that residual TLR ligands present in the ViPS preparation used for making typhoid subunit vaccines account for the robust immune response generated by these vaccines. I show the presence of endotoxin, a potent agonist of TLR4, in ViPS preparations and ViPS vaccines. Furthermore, I found that ViPS obtained from various sources induces the production of proinflammatory cytokines such as IL-6 from mouse peritoneal exudate cells. Unconjugated and tetanus toxoid-conjugated ViPS vaccines activate human and mouse TLR4. Mice deficient in TLR4 or the signaling adaptors MyD88 and Trif (Toll/IL-1R domain-containing adapter inducing IFN-β) are severely impaired in generating anti-ViPS responses to these vaccines. Elimination of the TLR4 agonist in ViPS preparation resulted in the loss of immunogenicity, and addition of lipid A, a known TLR4 agonist, restored the immunogenicity. These data highlight the importance of associated TLR ligands in the immunogenicity of ViPS subunit vaccines.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139099426","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}

{"title":"Lung Epithelial Regnase-1 Dampens Local Immune Response but Does Not Worsen Susceptibility to Klebsiella pneumoniae.","authors":"Becky Lin, Li Fan, Shaterra Jackson, Aidan R Matunis, Dequan Lou, Kong Chen, Giraldina Trevejo-Nuñez","doi":"10.4049/immunohorizons.2300082","DOIUrl":"10.4049/immunohorizons.2300082","url":null,"abstract":"<p><p>Klebsiella pneumoniae (KP) presents a global health threat, leading to significant morbidity and mortality due to its multidrug-resistant profile and the limited availability of therapeutic options. To eliminate KP lung infection, the host initiates a robust inflammatory response. One of the host's mechanisms for mitigating excessive inflammation involves the RNA-binding protein regnase-1 (Reg1, MCPIP1, or ZC3H12A). Reg1 has an RNA binding domain that recognizes stem-loop structures in the 3' untranslated region of various proinflammatory transcripts, leading to mRNA decay. However, excessive suppression of inflammation by Reg1 results in suboptimal KP control. Reg1 deficiency within the nonhematopoietic compartment confers resistance to KP in the lung. Given that lung epithelium is crucial for KP resistance, we hypothesized that selective deletion of Reg1 in lung epithelial cells might enhance proinflammatory signals, leading to a better control of KP. Our transcriptomic analysis of epithelial cells in KP-infected wild-type mice revealed the presence of three distinct alveolar type 2 cell (AT2) subpopulations (conventional, inflammatory, and cycling) and enrichment of Reg1 in inflammatory AT2 cells. We conditionally deleted Reg1 in lung AT2 cells (ΔReg1), which amplified the local inflammatory response in the lung and increased macrophage cell numbers compared with controls. However, when ΔReg1 mice were subjected to KP infection, there were no significant differences in bacterial burden or survival compared with controls. These findings suggest that the local inflammatory response enhanced by Reg1 deletion in AT2 cells is insufficient to control KP infection.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"89-96"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473043","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}

{"title":"Obesity-related Plasma CXCL10 Drives CX3CR1-dependent Monocytic Secretion of Macrophage Migration Inhibitory Factor.","authors":"Svenja Meyhöfer, Armin Steffen, Kirstin Plötze-Martin, Jens-Uwe Marquardt, Sebastian M Meyhöfer, Karl-Ludwig Bruchhage, Ralph Pries","doi":"10.4049/immunohorizons.2300114","DOIUrl":"10.4049/immunohorizons.2300114","url":null,"abstract":"<p><p>Obesity is characterized by excessive body fat accumulation and comorbidities such as diabetes mellitus, cardiovascular disease, and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS are associated with immune disturbance, alterations of systemic inflammatory mediators, and immune cell recruitment to metabolic tissues. Chemokine CXCL10 is an important regulator of proinflammatory immune responses and is significantly increased in patients with severe obesity. This research project aims to investigate the impact of CXCL10 on human monocytes in patients with obesity. We studied the distribution of the CD14/CD16 monocyte subsets as well as their CX3CR1 expression patterns in whole-blood measurements from 92 patients with obesity and/or OSAS with regard to plasma CXCL10 values and individual clinical parameters. Furthermore, cytokine secretion by THP-1 monocytes in response to CXCL10 was analyzed. Data revealed significantly elevated plasma CXCL10 in patients with obesity with an additive effect of OSAS. CXCL10 was found to drive monocytic secretion of macrophage migration inhibitory factor via receptor protein CX3CR1, which significantly correlated with the individual body mass index. Our data show, for the first time, to our knowledge, that CX3CR1 is involved in alternative CXCL10 signaling in human monocytes in obesity-related inflammation. Obesity is a multifactorial disease, and further investigations regarding the complex interplay between obesity-related inflammatory mediators and systemic immune balances will help to better understand and improve the individual situation of our patients.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"19-28"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089746","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}

{"title":"STAT1 Employs Myeloid Cell-Extrinsic Mechanisms to Regulate the Neutrophil Response and Provide Protection against Invasive Klebsiella pneumoniae Lung Infection.","authors":"Shekina Gonzalez-Ferrer, Hernán F Peñaloza, Rick van der Geest, Zeyu Xiong, Atish Gheware, Mohammadreza Tabary, Megan Kochin, Kathryn Dalton, Henry Zou, Dequan Lou, Karina Lockwood, Yingze Zhang, William G Bain, Rama K Mallampalli, Anuradha Ray, Prabir Ray, Daria Van Tyne, Kong Chen, Janet S Lee","doi":"10.4049/immunohorizons.2300104","DOIUrl":"10.4049/immunohorizons.2300104","url":null,"abstract":"<p><p>Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread bacterial dissemination and lung injury development. Yet, myeloid cell STAT1 was dispensable for control of KP proliferation and dissemination, because myeloid cell-specific STAT1-deficient (LysMCre/WT;Stat1fl/fl) mice showed bacterial burden in the lung, liver, and kidney similar to that of their wild-type littermates. Surprisingly, IL-17-producing CD4+ T cells infiltrated Stat1-/- murine lungs early during KP infection. The increase in Th17 cells in the lung was not due to preexisting immunity against KP and was consistent with circulating rather than tissue-resident CD4+ T cells. However, blocking global IL-17 signaling with anti-IL-17RC administration led to increased proliferation and dissemination of KP, suggesting that IL-17 provided by other innate immune cells is essential in defense against KP. Contrastingly, depletion of CD4+ T cells reduced Stat1-/- murine lung bacterial burden, indicating that early CD4+ T cell activation in the setting of global STAT1 deficiency is pathogenic. Altogether, our findings suggest that STAT1 employs myeloid cell-extrinsic mechanisms to regulate neutrophil responses and provides protection against invasive KP by restricting nonspecific CD4+ T cell activation and immunopathology in the lung.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"122-135"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577329","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}

{"title":"Gut Microbiota Is Associated with Onset and Severity of Type 1 Diabetes in Nonobese Diabetic Mice Treated with Anti-PD-1.","authors":"Shriram Patel, Eugenia Becker, Corinne Ploix, Guido Steiner, Petar Scepanovic, Matthias Fueth, Maria Cristina de Vera Mudry, Anne Eichinger-Chapelon, Estelle Marrer-Berger, Marcus J Claesson","doi":"10.4049/immunohorizons.2300103","DOIUrl":"10.4049/immunohorizons.2300103","url":null,"abstract":"<p><p>Our bodies are home to individual-specific microbial ecosystems that have recently been found to be modified by cancer immunotherapies. The interaction between the gut microbiome and islet autoimmunity leading to type I diabetes (T1D) is well described and highlights the microbiome contribution during the onset and T1D development in animals and humans. As cancer immunotherapies induce gut microbiome perturbations and immune-mediated adverse events in susceptible patients, we hypothesized that NOD mice can be used as a predictive tool to investigate the effects of anti-PD-1 treatment on the onset and severity of T1D, and how microbiota influences immunopathology. In this longitudinal study, we showed that anti-PD-1 accelerated T1D onset, increased glutamic acid decarboxylase-reactive T cell frequency in spleen, and precipitated destruction of β cells, triggering high glucose levels and pancreatic islet reduction. Anti-PD-1 treatment also resulted in temporal microbiota changes and lower diversity characteristic of T1D. Finally, we identified known insulin-resistance regulating bacteria that were negatively correlated with glucose levels, indicating that anti-PD-1 treatment impacts the early gut microbiota composition. Moreover, an increase of mucin-degrading Akkermansia muciniphila points to alterations of barrier function and immune system activation. These results highlight the ability of microbiota to readily respond to therapy-triggered pathophysiological changes as rescuers (Bacteroides acidifaciens and Parabacteroides goldsteinii) or potential exacerbators (A. muciniphila). Microbiome-modulating interventions may thus be promising mitigation strategies for immunotherapies with high risk of immune-mediated adverse events.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"872-885"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038347","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}

{"title":"Side-by-Side Comparison of Compensation Beads Used in Polychromatic Flow Cytometry.","authors":"Debajit Bhowmick, Sara K Lowe, Michelle L Ratliff","doi":"10.4049/immunohorizons.2300066","DOIUrl":"10.4049/immunohorizons.2300066","url":null,"abstract":"<p><p>Compensation or unmixing is essential in analyzing multiparameter flow cytometry data. Errors in data correction, either by compensation or unmixing, can completely change the outcome or mislead the researchers. Owing to limited cell numbers, researchers often use synthetic beads to generate the required single stains for the necessary calculation. In this study, the capacity of synthetic beads to influence data correction is evaluated. Corrected data for human peripheral blood cells were generated using cell-based compensation from the same cells or bead-based compensation to identify differences between the methods. These data suggest that correction with beads on full-spectrum and conventional cytometers does not always follow the basic flow compensation/unmixing expectations and alters the data. Overall, the best approach for bead-based correction for an experiment is to evaluate which beads and fluorochromes are most accurately compensated/unmixed.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"819-833"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500617","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}

{"title":"No Evidence That Analgesic Use after COVID-19 Vaccination Negatively Impacts Antibody Responses.","authors":"Bonnie J Lafleur, Lisa White, Michael D Dake, Janko Z Nikolich, Ryan Sprissler, Deepta Bhattacharya","doi":"10.4049/immunohorizons.2300090","DOIUrl":"10.4049/immunohorizons.2300090","url":null,"abstract":"<p><p>Uptake of mRNA vaccines, especially booster immunizations, against COVID-19 has been lower than hoped, perhaps in part due to their reactogenicity. Analgesics might alleviate symptoms associated with vaccination, but they might also impact immune responses. We semiquantitatively measured Ab responses following COVID-19 vaccination in 2354 human participants surveyed about analgesic use after vaccination. Participants who used nonsteroidal anti-inflammatory drugs or acetaminophen after vaccination showed elevated Ab levels against the receptor-binding domain of Spike protein relative to those who did not use analgesics. This pattern was observed for both mRNA-1273 and BNT162b2 and across age groups. Participants who used analgesics more frequently reported fatigue, muscle aches, and headaches than did those who did not use painkillers. Among participants who reported these symptoms, we observed no statistically significant differences in Ab levels irrespective of analgesic use. These data suggest that elevated Ab levels are associated with symptoms and inflammatory processes rather than painkiller use per se. Taken together, we find no evidence that analgesic use reduces Ab responses after COVID-19 vaccination. Recommendation of their use to alleviate symptoms might improve uptake of booster immunizations.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"834-841"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815116","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}