IFI16 (the murine homologue is IFI204) is an intracellular double-stranded DNA (dsDNA) pattern recognition receptor (PRR) that plays a crucial role in bridging innate and adaptive immunity. However, its function in dendr...IFI16 (the murine homologue is IFI204) is an intracellular double-stranded DNA (dsDNA) pattern recognition receptor (PRR) that plays a crucial role in bridging innate and adaptive immunity. However, its function in dendritic cell (DC) activation and anti-hepatocellular carcinoma (HCC) efficacy remains poorly characterised. This study demonstrates that IFI16 promotes DC maturation, functional activation and antitumor immunity. This effect occurs through activation of the STING-TBK1-IRF3 signalling pathway. Our findings establish IFI16 as a key molecule enabling DCs to sense dsDNA and initiate antitumor responses. Consequently, targeting IFI16 and its downstream STING-TBK1-IRF3 signalling pathway represents a potential therapeutic strategy for hepatocellular carcinoma.
Leishmania infections profoundly reshape host immunity, yet their impact on central T-cell development remains underappreciated. The thymus, a key site for establishing a functional and self-tolerant T-cell repertoire, i...Leishmania infections profoundly reshape host immunity, yet their impact on central T-cell development remains underappreciated. The thymus, a key site for establishing a functional and self-tolerant T-cell repertoire, is highly sensitive to systemic inflammatory cues. Growing evidence indicates that parasitic diseases, including leishmaniasis, can perturb thymic structure and function through direct parasite presence or sustained inflammatory stress. Such disturbances may alter thymocyte maturation, leading to reduced T-cell output and the release of cells with aberrant specificity. Beyond compromising protective immunity, these changes may create conditions favourable to immune dysregulation, including the emergence of autoimmune manifestations and a microenvironment permissive to malignant transformation. This narrative review synthesises current findings on how Leishmania interacts with immunological tissues and highlights the thymus as a potential and overlooked target whose dysfunction may bridge infection, autoimmunity and cancer.
Bovine respiratory disease (BRD) remains a major health and economic challenge for the cattle industry, driven by the interplay of viral and bacterial pathogens that compromise animal welfare, productivity and antimicrob...Bovine respiratory disease (BRD) remains a major health and economic challenge for the cattle industry, driven by the interplay of viral and bacterial pathogens that compromise animal welfare, productivity and antimicrobial stewardship. Among the primary viral agents, Bovine herpesvirus 1 (BoHV-1) and Bovine respiratory syncytial virus (BRSV) play critical roles in initiating and exacerbating respiratory pathology. In this study, we engineered two recombinant Bovine herpesvirus 4 (BoHV-4)-based vectors encoding chimeric antigens based on BoHV-1 glycoprotein D (gD) and BRSV fusion glycoprotein (gF), with the goal of developing a multivalent vaccine platform. Immunological evaluation in a murine model demonstrated that both vaccine constructs elicited robust humoral and cell-mediated immune responses directed against both pathogens. Vaccination induced neutralising antibodies capable of inhibiting BoHV-1 and BRSV infection, as well as antigen-specific T-cell responses that mediated cytotoxic activity against target cells expressing either antigen. These findings provide proof-of-concept that chimeric antigens are effective in eliciting humoral and cellular immune response toward two main different pathogens, BoHV-1 and BRSV, and BoHV-4 is a versatile vector for the delivery of heterologous antigens. The demonstrated ability to induce both virus neutralisation and cytotoxic T-cell activity supports the further development of BoHV-4-vectored bivalent vaccines for BRD control, with potential application at improving livestock health and reducing reliance on antimicrobial treatments. Moreover, the present study highlights BoHV-4-based vectors and chimeric peptides as a promising bivalent vaccine platform potentially translatable for controlling similar viruses like human respiratory syncytial virus (hRSV) and varicella zoster virus (VZV) across human populations.
Feng K, Chang L, Yan Y
… +11 more, Sun H, Liu Y, Song S, Nuermaimaiti A, Halemubieke S, Mei L, Su Q, Liu X, Lu Z, Ji H, Wang L
BMC Immunol
· 2026 May · PMID 42135629
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The Human Leukocyte Antigen (HLA) system is a key component of the immune system, involving aspects such as autoimmune reactions, transplant rejection reactions, and related diseases. HLA typing technology enables precis...The Human Leukocyte Antigen (HLA) system is a key component of the immune system, involving aspects such as autoimmune reactions, transplant rejection reactions, and related diseases. HLA typing technology enables precise decision-making in clinical tissue matching, disease susceptibility assessment, and drug response prediction. Therefore, this article summarizes the genetic characteristics of HLA, several commonly used methods for typing, including serological methods and molecular biology methods. It also explores the clinical applications of HLA typing, such as in organ and stem cell transplantation, blood transfusion, and disease association studies. In addition, in recent years, the combination of Single Nucleotide Polymorphism (SNP) and PCR technology has shown its potential application in various gene typing. In particular, the application of SNP-PCR method in HLA typing provides new possibilities for improving typing accuracy, reducing costs, and shortening detection time. Therefore, we summarize the existing HLA typing technologies and prospects for the future development of SNP-PCR method in HLA typing. With the continuous progress of bioinformatics and high-throughput sequencing technology, SNP-PCR is expected to become an efficient, economical, and widely used method for HLA typing, providing strong support for precision medicine. In addition, combined with big data analysis, SNP-PCR is expected to further reveal the complex associations between HLA and various diseases, thereby promoting in-depth research and development in immunology, genetics, and clinical medicine.
Wiskott-Aldrich Syndrome protein (WASp) is an actin nucleation-promoting factor that regulates the dynamic rearrangements of the actin cytoskeleton following T cell receptor (TCR) engagement. Recognition of antigen by T...Wiskott-Aldrich Syndrome protein (WASp) is an actin nucleation-promoting factor that regulates the dynamic rearrangements of the actin cytoskeleton following T cell receptor (TCR) engagement. Recognition of antigen by T cells leads to TCR signal transduction, which involves the phosphorylation of various proteins in close proximity to the TCR, known as proximal TCR signalling. Proximal TCR signalling is initiated by the phosphorylation of signalling proteins including CD3 subunits, lymphocyte-specific protein tyrosine kinase (Lck) and zeta-chain-associated protein kinase 70 (ZAP70). Activation of these proteins initiates the formation of a signalosome, which is required for actin polymerisation and gene expression. The role of WASp in relation to proximal TCR signalling is largely unknown. In the present study, we knocked out WASp in Jurkat T cells using the CRISPR-Cas9 system to evaluate its effect on proximal TCR signalling. As expected, Jurkat T cells lacking WASp exhibited impaired actin polymerisation. Following TCR triggering, phosphorylation of CD3, Lck and ZAP70 was markedly reduced. There was also a failure in the recruitment of Lck and ZAP70 to the TCR. Impaired proximal TCR signalling (reduced tyrosine phosphorylation of CD3, Lck and ZAP70) was exclusively associated with decreased CD69 and CD25 expression. Therefore, besides its role in actin rearrangement, WASp is also required for proximal TCR signalling.
González de Castro C, Ruiz Rebollo ML, Cal-Sabater P
… +8 more, Arribas-Rodríguez E, Martín-Muñoz Á, Gonzalez Del Hierro A, Perez Mazzali M, Matesanz-Isabel J, Gonzalo-Benito H, Cuesta-Sancho S, Bernardo D
Acute pancreatitis (AP) patients can be classified into mild or severe outcome based on the presence of organ failure days during hospitalization. However, there are no biomarkers that can predict severity outcome. This...Acute pancreatitis (AP) patients can be classified into mild or severe outcome based on the presence of organ failure days during hospitalization. However, there are no biomarkers that can predict severity outcome. This study aim is to perform an unbiased characterization of the circulating immunome of AP patients at hospital admission aiming to identify novel biomarkers which could predict disease outcome prior to the onset of organ damage and clinical deterioration. Peripheral blood mononuclear cells (PBMC) were collected from newly hospitalized AP patients. Based on their evolution, patients were classified following the Modified Atlanta classification into mild acute pancreatitis (mAP) (n = 20) as well as moderately and/or severe acute pancreatitis (ms-sAP) (n = 20). PBMC were analysed by high-dimensional spectral cytometry with unsupervised dimensionality reduction and clustering algorithms based on the subsequent outcome of the patients. Results were further validated by classical gating and functional approaches with a smaller cohort (n = 8 mAP and n = 8 ms-sAP). A total of 120 different immune cell clusters were identified and characterized in AP patients at hospitalization. Following computational analysis and classical gating validation approaches, circulating CD2CD8 NKT-Like cells were found to be specifically reduced in ms-sAP patients. Moreover, NKT-Like cell subsets from these patients displayed an IL-15 induced expansion of NKG2a and NKp30 referred to mAP. Patients with AP at hospitalization with subsequent ms-sAP display a specific reduction of NKT-Like cells coupled with an expanded function. Hence, quantifying the phenotype and/or function of circulating NKT-Like cells during hospital admission could serve as a predictive biomarker for AP severity, aiding in early stratification and personalized treatment strategies.
Immunotherapy has revolutionised the clinical treatment of many types of cancer, including immune checkpoint inhibitors, adoptive cell therapies, and tumour vaccines, which are capable of providing long-term clinical ben...Immunotherapy has revolutionised the clinical treatment of many types of cancer, including immune checkpoint inhibitors, adoptive cell therapies, and tumour vaccines, which are capable of providing long-term clinical benefit in some patients. Nevertheless, a high degree of tumour immune heterogeneity and an ongoing immunosuppressive the tumour microenvironment (TME) remain as limitations to therapeutic outcomes, and alternative methods to stimulate antitumor immunity are necessary. Given these limitations, recent researchers has been attracted to the fact that Toxoplasma gondii and its derivatives can be considered as unconventional parasite-derived immunomodulatory vectors in cancer immunotherapy. T. gondii infection triggers strong Th1 immunity mediated on interleukin-12 (IL-12) and interferon-γ (IFN-γ), promotes dendritic cell maturation, and activates cytotoxic T cells, thus reprogramming the TME to a more immunostimulatory condition. Attenuated or metabolic-deficient strains have shown strong antitumor efficacy in various murine tumour models by reducing tumour burden and prolonging host survival. Meanwhile, the effector proteins of the parasite, such as GRA15, GRA16, and ROP18, regulate immune cell function to induce tumour cell apoptosis, inhibit angiogenesis, and suppress metastasis. The T. gondii-infected cell-derived exosomes and T. gondii lysate antigens are also immunogenic and represent safer, non-infectious therapeutic alternatives. Here, we summarise the latest advances in the antitumor effects of T. gondii and its derivatives, focusing on immune activation, signalling regulation, direct antitumor effects, synergistic immunotherapy, potential for drug development, and challenges in future clinical translation. T. gondii and its derivatives have shown the potential to reshape TME and convert 'cold' tumours into 'hot' ones in murine cancer models. We believe that with further research in this field, the future of cancer immunotherapy will see breakthrough advancements.
Chu W, Zhang Y, Shen S
… +5 more, Wang Z, Guo Y, Yu Y, Huang D, Davtyan N
BMC Immunol
· 2026 May · PMID 42106605
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BACKGROUND: Periodontitis is a long-lasting inflammatory disorder of structures attached, which is significantly influenced by insufficient or dysregulated immune responses. Mesenchymal stem cells (MSCs) and their extrac...BACKGROUND: Periodontitis is a long-lasting inflammatory disorder of structures attached, which is significantly influenced by insufficient or dysregulated immune responses. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) are a promising therapeutic modality. This study explores the therapeutic efficacy of EVs derived from miR-146a-overexpressing bone marrow-derived mesenchymal stem cells (BMSCs) in a ligature-induced periodontitis model. RESULTS: BMSCs were transfected to overexpress miR-146a, and their EVs were isolated. Periodontitis was induced in 30 female C57Bl/6 mice and divided into three groups: a control group receiving PBS, a miR-control EV-treated group, and a miR-146a-EV-treated group. EVs were administered subgingivally, and clinical parameters were evaluated. Levels of proinflammatory cytokines interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, and IL-6, as well as anti-inflammatory cytokines IL-10, IL-4, and transforming growth factor (TGF)-β, were quantified using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR). Phosphorylated p38, JNK, ERK1/2, and NF-κB p65 were also quantified by ELISA, and TRAF6 and IRAK1 mRNA and protein levels were assessed to evaluate inflammatory signaling pathways. In the gingival tissue and systemic circulation, the proinflammatory cytokines IL-1β, IL-8, TNF-α, and IL-6 were significantly downregulated, while the levels of the anti-inflammatory mediators IL-10, IL-4, and TGF-β were significantly increased in the miR-146a-EV group when compared with the control group. miR-146a-EV treatment significantly reduced MAPK and NF-κB activation while downregulating TRAF6 and IRAK1 expression in gingival tissues. CONCLUSION: miR-146a-transduced MSC-derived EVs ameliorated ligature-induced periodontitis by modulating local and systemic cytokine expression. These results indicate that miR-146a-EVs can be a novel, cell-free therapy for the treatment of periodontitis.
Dendritic cells (DCs) are rare in human blood, often requiring enrichment prior to analysis. Here, we benchmark commonly used pan-DC enrichment methods by comparing recovered DC subset composition to ex vivo references....Dendritic cells (DCs) are rare in human blood, often requiring enrichment prior to analysis. Here, we benchmark commonly used pan-DC enrichment methods by comparing recovered DC subset composition to ex vivo references. While all approaches capture major DC populations, recovery is partial and exhibits method-dependent, subset-specific biases. These differences alter the apparent DC composition and may influence downstream analyses. Created with BioRender.com.
BMC Immunol
· 2026 May · PMID 42104232
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Functional dyspepsia (FD) is a prevalent gastrointestinal disorder in children, but its underlying molecular mechanisms remain poorly understood. Mitochondrial dysfunction and excessive mitophagy have been implicated in...Functional dyspepsia (FD) is a prevalent gastrointestinal disorder in children, but its underlying molecular mechanisms remain poorly understood. Mitochondrial dysfunction and excessive mitophagy have been implicated in FD, but the underlying mechanisms remain poorly understood. This study aimed to investigate the role of SIRT1 in mitochondrial quality control and its potential therapeutic value in pediatric FD. Serum samples from pediatric FD patients and healthy controls were analyzed for SIRT1 expression and inflammatory cytokines. Human gastric smooth muscle cells (HGSMCs) were treated with carbonyl cyanide m-chlorophenyl hydrazone (CCCP) to induce mitochondrial stress. Mitochondrial function, mitophagy, oxidative stress, and protein interactions were assessed using qPCR, Western blot, co-immunopcipitation, and functional assays including ATP levels, mitochondrial membrane potential, ROS, MDA, SOD, and GSH-Px. The results showed that SIRT1 was significantly downregulated in both pediatric FD patient sera and CCCP-stimulated HGSMCs, accompanied by elevated pro-inflammatory cytokines including IL-6, TNF-α, and IL-1β. Overexpression of SIRT1 improved cell viability, ATP production, mitochondrial membrane potential, and suppressed excessive mitophagy and oxidative stress. Conversely, DRP1 knockdown phenocopied the protective effects of SIRT1, reducing mitophagy and oxidative stress in CCCP-stimulated cells. SIRT1 directly interacted with DRP1 and promoted its deacetylation at lysine 283, leading to accelerated DRP1 degradation. Rescue experiments confirmed that DRP1 overexpression reversed the protective effects of SIRT1 on mitochondrial function and redox homeostasis. In conclusion, SIRT1 exerts protective effects in pediatric FD by deacetylating DRP1 at K283, thereby inhibiting excessive mitophagy and ameliorating mitochondrial dysfunction and oxidative stress. These findings identify the SIRT1-DRP1 axis as a potential therapeutic target for pediatric FD.
Zheng T, Ye M, Yang Y
… +7 more, Yao L, Zou D, Liao C, Feng X, Tian T, Tang Z, Zhou P
BMC Immunol
· 2026 May · PMID 42104222
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BACKGROUND: Treponema pallidum (T. pallidum) can invade various organs and tissues. However, there have been few studies on the pathological injury of T. pallidum to the testis and sperm. The NOD-like receptor protein 3...BACKGROUND: Treponema pallidum (T. pallidum) can invade various organs and tissues. However, there have been few studies on the pathological injury of T. pallidum to the testis and sperm. The NOD-like receptor protein 3 (NLRP3) inflammasome, upon activation, leads to pyroptosis-a programmed, pro-inflammatory cell death process, and promotes inflammatory responses. Previous investigations have found that the NLRP3 inflammasome is elevated in the testis tissues of rabbits infected with T. pallidum. This study aimed to investigate whether T. pallidum induced pathological injury of the rabbit testis and sperm through NLRP3 inflammasome-mediated pyroptosis. METHODS: While rabbits in the T. pallidum group received an intratesticular injection of 1 mL of a bacterial suspension containing 10⁷/mL treponemes, those in the sham group were administered an equal volume of normal saline to serve as the injection procedure control. 14 days later, testis tissues were harvested for IHC and H&E staining, and analysis of qPCR. In vitro, GC-2spd cells were stimulated by T. pallidum (MOI = 20). After administering MCC950, the expression levels of the inflammasome NLRP3 and downstream pyroptosis-related molecules were subsequently detected. RESULTS: T. pallidum caused obvious pathological damage to the rabbit testis and sperm reduction. Meanwhile, the gene expression levels of NLRP3, ASC, GSDMD, Caspase-1, IL-Iβ, and IL-18 in the T. pallidum group were higher than those of the sham group. Additionally, T. pallidum induced cell injury and pyroptosis in GC-2spd cells, which was improved by the NLRP3 inflammasome inhibitor MCC950. CONCLUSIONS: Our findings validated that T. pallidum induced pathological damage to the testis and sperm reduction via NLRP3 inflammasome activation and pyroptosis. By specifically inhibiting the NLRP3 inflammasome, MCC950 has the potential to ameliorate sperm cell damage under in vitro conditions via the blockade of pyroptotic cell death.
During an immune response, T cells face one of the most consequential decisions of their lifespan upon recognition of a ligand they have not previously encountered: whether to exit the naive basal state, undergo clonal e...During an immune response, T cells face one of the most consequential decisions of their lifespan upon recognition of a ligand they have not previously encountered: whether to exit the naive basal state, undergo clonal expansion and acquire effector functions. This process is often portrayed as a binary switch, in which naive cells from a highly diverse repertoire transition from an 'off' state to an 'on' state. However, this digital view overlooks the crucial prior information that T cells integrate through T cell receptor (TCR) interactions with self-peptide-MHC (self-pMHC). During thymic selection, immature T cells encounter a unique self-pMHC ligandome that shapes their development. After maturation, naive T cells continue to engage self-ligands as they patrol secondary lymphoid organs. Here we review evidence that these encounters with self-peptides are not only essential for T cell survival but also have lasting consequences that dynamically tune T cell function when called into action. The naive off state, therefore, is neither fixed nor functionally neutral. We argue that a deeper understanding of an individual's self-peptide repertoire is crucial for deciphering TCR self and non-self discrimination and for effectively harnessing T cell responses to foreign antigens.
BMC Immunol
· 2026 May · PMID 42098601
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OBJECTIVE: This study aimed to investigate serum levels of tumor necrosis factor-alpha (TNF-α) in patients with immune-mediated necrotizing myopathy (IMNM) and to explore its correlation with disease activity. METHODS: S...OBJECTIVE: This study aimed to investigate serum levels of tumor necrosis factor-alpha (TNF-α) in patients with immune-mediated necrotizing myopathy (IMNM) and to explore its correlation with disease activity. METHODS: Serum TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). TNF-α mRNA expression in muscle tissues from IMNM patients was detected by reverse transcription quantitative real-time PCR (RT-qPCR). In vitro experiments were performed on human muscle cells stimulated with TNF-α to assess cell viability and the expression of downstream molecules. RESULTS: Serum TNF-α levels were significantly elevated in IMNM patients compared to healthy controls (p = 0.0002). In IMNM patients, TNF-α levels showed a significant positive correlation with serum creatine kinase (CK; p = 0.0004) and lactate dehydrogenase (LDH; p = 0.0137). TNF-α mRNA was also overexpressed in muscle biopsies from patients with IMNM. In vitro, TNF-α stimulation significantly reduced muscle cell viability and upregulated the mRNA expression of downstream inflammatory mediators, including IP-10, MCP-1, IL-6, and phosphorylated p65. CONCLUSION: Elevated serum TNF-α in IMNM patients is associated with muscle damage and may contribute to disease pathogenesis by amplifying the inflammatory response. These findings suggest that TNF-α could serve as a potential biomarker for assessing disease severity in IMNM.
BMC Immunol
· 2026 May · PMID 42092763
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BACKGROUND: Severe pneumonia (SP) is a critical infectious disease characterized by excessive inflammatory responses, and the molecular mechanisms underlying its progression remain incompletely understood. OBJECTIVE: To...BACKGROUND: Severe pneumonia (SP) is a critical infectious disease characterized by excessive inflammatory responses, and the molecular mechanisms underlying its progression remain incompletely understood. OBJECTIVE: To investigate the expression pattern, diagnostic value, and potential functional regulatory mechanisms of miR-200b in SP. METHODS: RT-qPCR was used to detect miR-200b expression levels; ROC curve analysis was used to evaluate its diagnostic performance; prognostic indicators of miR-200b were compared between high- and low-expression groups, and Cox regression was employed to identify independent prognostic factors. In vitro validation of the pro-inflammatory effects of miR-200b. Target genes were identified through Venn diagram-based prediction and dual luciferase reporter assays. Functional recovery experiments were conducted to elucidate regulatory pathways. RESULT: miR-200b expression was significantly higher in SP patients than in CP/HC groups, with an ROC curve AUC of 0.848 distinguishing SP from CP/HC, demonstrating good diagnostic performance. Elevated miR-200b expression significantly correlated with poorer prognostic indicators and served as an independent risk factor for adverse SP outcomes. In vitro experiments demonstrated that miR-200b expression was upregulated in a concentration- and time-dependent manner following LPS stimulation, promoting IL-6 and TNF-α secretion. RHOA was identified as a direct target gene of miR-200b, and miR-200b exerts pro-inflammatory effects by inhibiting RHOA and activating the NF-κB pathway. CONCLUSION: miR-200b serves as a potential diagnostic and prognostic biomarker for SP. By targeting RHOA to activate the NF-κB pathway, it promotes inflammatory damage in SP, thus providing a novel therapeutic target for clinical intervention.
Caspase activation platforms such as the apoptosome, inflammasome and PIDDosome are central to cellular responses to stress, coordinating inflammation, cell death and cell differentiation. Although each of these complexe...Caspase activation platforms such as the apoptosome, inflammasome and PIDDosome are central to cellular responses to stress, coordinating inflammation, cell death and cell differentiation. Although each of these complexes has been extensively studied in isolation, a comparative understanding of their structural and functional principles is lacking. Here we provide an integrated review of the architecture, activation mechanisms and signalling outputs of these supramolecular signalling platforms. All three of these platforms share a broadly conserved domain architecture and promote proximity-induced caspase activation, but they differ in their subcellular localization and upstream triggers. Furthermore, we explore differences in their downstream effectors and roles in immune signalling, cell cycle regulation and tissue homeostasis. Germline mutations in humans affecting these complexes are linked to cancer predisposition, immune dysregulation and neurodevelopmental disorders, respectively. Finally, we discuss therapeutic opportunities and unresolved questions, aiming to stimulate cross-disciplinary research and translational applications.
Once considered to be passive oxygen carriers, erythroid cells are now recognized as dynamic modulators of immune responses. Erythroid progenitors and precursors, collectively known as CD71⁺ erythroid cells, can suppress...Once considered to be passive oxygen carriers, erythroid cells are now recognized as dynamic modulators of immune responses. Erythroid progenitors and precursors, collectively known as CD71⁺ erythroid cells, can suppress innate and adaptive immune responses in neonates, in mothers during pregnancy, in chronic conditions such as cancer and autoimmunity, and during infection with viruses, including SARS-CoV-2 and HIV. Mature red blood cells engage pathogens directly, scavenge chemokines, cytokines and nucleic acids, and modulate immune functions through redox buffering and receptor-mediated interactions. The immune effects of red blood cells are highly context dependent, ranging from suppression to activation. This Review highlights the emerging field of erythroid-immune crosstalk and its translational potential in the settings of infection, cancer, pregnancy and chronic inflammatory conditions.