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Conventional dendritic cells (cDC) are central to maintaining the balance between protective immune responses and tolerance to harmless antigens, especially in the intestine. Short chain fatty acids (SCFAs) such as butyrate play critical roles in regulating intestinal immunity, but the underlying mechanisms remain unclear. Here we demonstrate that microbiota-derived butyrate alters intestinal cDC populations in vivo resulting in decreased numbers of the cDC2 lineage. By establishing a novel in vitro culture model, we show that butyrate has a direct and selective ability to repress the development of cDC2 from cDC precursors, an effect that is independent of G-protein coupled receptors (GPCRs) and is due to inhibition of histone deacetylase 3. Finally, cDC derived from pre-cDC in the presence of butyrate in vitro express lower levels of costimulatory molecules and have a decreased ability to prime naïve T cells. Together, our data show that butyrate affects the developmental trajectory of cDC, selectively repressing the cDC2 lineage and reducing their ability to stimulate T cells. These properties may help explain the ability of butyrate to maintain homeostasis in the intestine.
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BACKGROUND: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. METHODS: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. RESULTS: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rhoâ =â 0.70; P = .016). Microbiota structure (ß diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. CONCLUSIONS: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.
Treatment of active Crohn's disease with exclusive enteral nutrition diminishes the proinflammatory potential of fecal microbial components, hence suggesting a mechanism of action involving modulation of diet-dependent microbes and their products that cause gut inflammation.
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Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.
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Artrite Experimental , Colágeno Tipo II , Microbioma Gastrointestinal , Homeostase , Animais , Artrite Experimental/imunologia , Artrite Experimental/prevenção & controle , Colágeno Tipo II/imunologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Articulações/imunologia , Articulações/efeitos dos fármacos , Articulações/patologia , Camundongos Endogâmicos DBA , Interleucina-17/metabolismo , Interleucina 22 , Administração OralRESUMO
BACKGROUND: The immunological effects of treatment with exclusive enteral nutrition (EEN) in Crohn's disease (CD) remain unknown. We characterized the plasma levels of inflammation-related proteins (IRPs) in children with CD and ulcerative colitis (UC) compared with noninflammatory controls (non-IBD) and explored the effect of EEN in CD. METHODS: Ninety-two IRPs were quantified using Olink proteomics in children with CD (nâ =â 53), UC (nâ =â 11), and non-IBD (nâ =â 19). For 18 children with active CD, IRPs were measured before and after 8 weeks of EEN. Relationships with disease phenotype and response to EEN were studied. RESULTS: Compared with non-IBD, patients with active UC and CD had different levels of 27 (24 raised, 3 decreased) and 29 (26 raised, 3 decreased) IRPs, respectively. Exclusive enteral nutrition modified the levels of 19 IRPs (13 increased, 6 decreased including CCL23, interleukin-24, interleukin-6, and MMP-1). More pronounced changes in IRP profile were observed in patients with ileal involvement and a ≥50% decrease in fecal calprotectin during EEN compared with those with colonic involvement and a <50% decrease in fecal calprotectin, respectively. A machine-learning model utilizing baseline IRP profile predicted response to EEN with a sensitivity of 89%, specificity of 57%, and accuracy of 73%. Thymic stromal lymphopoietin was the most important IRP in the model, this being higher in responders. CONCLUSIONS: Inflammation-related proteins may be useful in the differential diagnosis of IBD. Exclusive enteral nutrition extensively modulated IRPs levels in children with active CD with more pronounced effects observed in patients who showed a reduction in FC and had ileal disease involvement.
Plasma inflammation-related proteins are altered in children with inflammatory bowel disease. In active Crohn's disease, exclusive enteral nutrition modified several of these proteins, particularly in disease involving the ileum and in patients whose fecal calprotectin levels significantly decreased.
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The immunological effects of exclusive enteral nutrition (EEN) in the treatment of active Crohn's disease (CD) are yet to be unveiled. The present study investigated changes in peripheral blood mononuclear cell profiles in children with active CD following 8-week treatment with EEN. In nine children, EEN significantly decreased the number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA, with corresponding increases observed in the frequency of circulating central and effector memory CD8+ T cells. These signals were conserved when looking at a subgroup of patients who achieved remission, and another who demonstrated the highest level of compliance to EEN. We speculate that the increases in circulating central and effector memory CD8+ T cells may be related to the extensive microbiome-modifying effects of EEN dampening immune response within the gastrointestinal tract.
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Doença de Crohn , Nutrição Enteral , Leucócitos Mononucleares , Humanos , Doença de Crohn/terapia , Doença de Crohn/imunologia , Doença de Crohn/sangue , Nutrição Enteral/métodos , Criança , Masculino , Feminino , Adolescente , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Linfócitos T CD8-Positivos/imunologia , Microbioma GastrointestinalRESUMO
BACKGROUND: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization. OBJECTIVES: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD. METHODS: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR). RESULTS: Of 37 patients recruited, 15 responded (FCal < 250 µg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (µmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN. CONCLUSIONS: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.
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Doença de Crohn , Microbiota , Criança , Humanos , Doença de Crohn/terapia , Doença de Crohn/metabolismo , Nutrição Enteral , Estudos Prospectivos , Indução de Remissão , Metaboloma , Butiratos , Acetatos , FenilacetatosRESUMO
Colorectal cancer (CRC) is the third most prevalent cancer worldwide with a high mortality rate (20-30%), especially due to metastasis to adjacent organs. Clinical responses to chemotherapy, radiation, targeted and immunotherapies are limited to a subset of patients making metastatic CRC (mCRC) difficult to treat. To understand the therapeutic modulation of immune response in mCRC, we have used a genetically engineered mouse model (GEMM), "KPN", which resembles the human 'CMS4'-like subtype. We show here that transforming growth factor (TGF-ß1), secreted by KPN organoids, increases cancer cell proliferation, and inhibits splenocyte activation in vitro. TGF-ß1 also inhibits activation of naive but not pre-activated T cells, suggesting differential effects on specific immune cells. In vivo, the inhibition of TGF-ß inflames the KPN tumors, causing infiltration of T cells, monocytes and monocytic intermediates, while reducing neutrophils and epithelial cells. Co-inhibition of TGF-ß and PD-L1 signaling further enhances cytotoxic CD8+T cells and upregulates innate immune response and interferon gene signatures. However, simultaneous upregulation of cancer-related metabolic genes correlated with limited control of tumor burden and/or progression despite combination treatment. Our study illustrates the importance of using GEMMs to predict better immunotherapies for mCRC.
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Neoplasias do Colo , Neoplasias Retais , Camundongos , Animais , Humanos , Fator de Crescimento Transformador beta1 , Fator de Crescimento Transformador beta/metabolismo , Interferons , Antígeno B7-H1/genética , Linfócitos T Citotóxicos/metabolismoRESUMO
BACKGROUND AND AIMS: Treatment adherence is key to the efficacy of exclusive enteral nutrition [100% EN] in active Crohn's disease [CD], but there are no biomarkers to objectively estimate this. We explored faecal parameters as biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive Enteral Nutrition Index of Compliance [GENIE]. METHODS: Healthy adults replaced all [100% EN] or part [85% EN, 50% EN, 20% EN] of their diet with a formula for 7 days. Faecal pH, water content, short chain fatty acids, and branched chain fatty acids [BCFAs] were measured before [D0] and after [D7] each intervention. Optimal biomarkers and threshold values were derived using receiver operating characteristic curve analyses and machine learning to develop the GENIE. The GENIE was then validated in 30 CD children, during and after 100% EN. RESULTS: In all, 61 adults were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN fromâ <100% EN. Two models were generated; one included faecal metabolites (Laboratory GENIE, L-GENIE; sensitivity, specificity, and positive predictive value [PPV] of 88%, 94%, and 92%) and a second one [Clinical Genie, C-GENIE] which considers only faecal pH [sensitivity, specificity, and PPV of 84%, 86%, and 81%]. Validation of GENIE in CD children found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity, and PPV of 85%, 88%, and 88%, respectively. CONCLUSIONS: GENIE can help predict adherence to 100% EN and may complement current conventional dietary assessment.
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The murine serous cavities contain a rare and enigmatic population of short-lived F4/80lo MHCII+ macrophages but what regulates their development, survival, and fate is unclear. Here, we show that mature F4/80lo MHCII+ peritoneal macrophages arise after birth, but that this occurs largely independently of colonization by microbiota. Rather, microbiota specifically regulate development of a subpopulation of CD11c+ cells that express the immunoregulatory cytokine RELM-α, are reliant on the transcription factor EGR2, and develop independently of the growth factor CSF1. Furthermore, we demonstrate that intrinsic expression of RELM-α, a signature marker shared by CD11c+ and CD11c- F4/80lo MHCII+ cavity macrophages, regulates survival and differentiation of these cells in the peritoneal cavity in a sex-specific manner. Thus, we identify a previously unappreciated diversity in serous cavity F4/80lo MHCII+ macrophages that is regulated by microbiota, and describe a novel sex and site-specific function for RELM-α in regulating macrophage endurance that reveals the unique survival challenge presented to monocyte-derived macrophages by the female peritoneal environment.
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Antígeno CD11c , Proteína 2 de Resposta de Crescimento Precoce , Macrófagos Peritoneais , Microbiota , Animais , Antígeno CD11c/metabolismo , Diferenciação Celular , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Feminino , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Caracteres SexuaisRESUMO
Type 2 immunity is activated in response to both allergens and helminth infection. It can be detrimental or beneficial, and there is a pressing need to better understand its regulation. The immunosuppressive cytokine IL-10 is known as a T helper 2 (Th2) effector molecule, but it is currently unclear whether IL-10 dampens or promotes Th2 differentiation during infection. Here we show that helminth infection in mice elicits IL-10 expression in both the intestinal lamina propria and the draining mesenteric lymph node, with higher expression in the infected tissue. In vitro, exogenous IL-10 enhanced Th2 differentiation in isolated CD4+ T cells, increasing expression of GATA3 and production of IL-5 and IL-13. The ability of IL-10 to amplify the Th2 response coincided with its suppression of IFNγ expression and in vivo we found that, in intestinal helminth infection, IL-10 receptor expression was higher on Th1 cells in the small intestine than on Th2 cells in the same tissue, or on any Th cell in the draining lymph node. In vivo blockade of IL-10 signalling during helminth infection resulted in an expansion of IFNγ+ and Tbet+ Th1 cells in the small intestine and a coincident decrease in IL-13, IL-5 and GATA3 expression by intestinal T cells. These changes in Th2 cytokines correlated with reduced expression of type 2 effector molecules, such as RELMα, and increased parasite egg production. Together our data indicate that IL-10 signalling promotes Th2 differentiation during helminth infection at least in part by regulating competing Th1 cells in the infected tissue.
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Helmintos , Interleucina-13 , Camundongos , Animais , Interleucina-13/metabolismo , Interleucina-10/metabolismo , Interleucina-5/metabolismo , Células Th2 , Células Th1 , Interferon gama/metabolismo , Citocinas/metabolismoRESUMO
Microbes exert influence across the microbiome-gut-brain axis through neurotransmitter production, induction of host immunomodulators, or the release or induction of other microbial or host molecules. Here, we used mass spectrometry imaging (MSI), a label-free imaging tool, to map molecular changes in the gut and brain in germ-free, antibiotic-treated and control mice. We determined spatial distribution and relative quantification of neurotransmitters and their precursors in response to the microbiome. Using untargeted MSI, we detected a significant change in the levels of four identified small molecules in the brains of germ-free animals compared to controls. However, antibiotic treatment induced no significant changes in these same metabolites in the brain after 1 week of treatment. This work exemplifies the utility of MSI as a tool for the study of known and discovery of novel, mediators of microbiome-gut-brain axis communication.
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Microbioma Gastrointestinal , Microbiota , Animais , Encéfalo/metabolismo , Eixo Encéfalo-Intestino , Microbioma Gastrointestinal/fisiologia , Espectrometria de Massas/métodos , CamundongosRESUMO
BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).
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Doença de Crohn , Nutrição Enteral , Criança , Doença de Crohn/terapia , Dieta , Humanos , Inflamação , Projetos Piloto , Indução de RemissãoRESUMO
Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.
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To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45+CD64+ HLA-DR+) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206+ macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206- macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
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Suscetibilidade a Doenças , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Biomarcadores , Suscetibilidade a Doenças/imunologia , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Imunidade nas Mucosas , Imunofenotipagem , Doenças Inflamatórias Intestinais/patologia , Interleucina-10/genética , Interleucina-10/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , TranscriptomaRESUMO
The use of bacteria as an alternative cancer therapy has been reinvestigated in recent years. SL7207: an auxotrophic Salmonella enterica serovar Typhimurium aroA mutant with immune-stimulatory potential has proven a promising strain for this purpose. Here, we show that systemic administration of SL7207 induces melanoma tumor growth arrest in vivo, with greater survival of the SL7207-treated group compared to control PBS-treated mice. Administration of SL7207 is accompanied by a change in the immune phenotype of the tumor-infiltrating cells toward pro-inflammatory, with expression of the TH 1 cytokines IFN-γ, TNF-α, and IL-12 significantly increased. Interestingly, Ly6C+ MHCII+ monocytes were recruited to the tumors following SL7207 treatment and were pro-inflammatory. Accordingly, the abrogation of these infiltrating monocytes using clodronate liposomes prevented SL7207-induced tumor growth inhibition. These data demonstrate a previously unappreciated role for infiltrating inflammatory monocytes underlying bacterial-mediated tumor growth inhibition. This information highlights a possible novel role for monocytes in controlling tumor growth, contributing to our understanding of the immune responses required for successful immunotherapy of cancer.
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Imunoterapia , Melanoma Experimental , Monócitos/imunologia , Salmonella typhimurium/imunologia , Células Th1/imunologia , Animais , Citocinas/imunologia , Feminino , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Camundongos , Salmonella typhimurium/genéticaRESUMO
The gut microbiota's function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development.
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Neurodegenerative diseases place a devastating burden on affected individuals and their families, and new treatments are desperately needed for these common immune-mediated inflammatory conditions. While large aggregates of abnormal proteins in the brain cause significant damage, it is becoming clear that smaller soluble protein aggregates can also contribute to disease, by both direct and indirect mechanisms. These soluble protein oligomers can be found in patients' serum. Here, we describe recent research that identifies effects of model oligomer molecules on peripheral blood T cells, therefore providing an additional mechanism by which neurodegeneration may be worsened through amplification of peripheral adaptive immune responses.
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Encéfalo/imunologia , Doenças Neurodegenerativas/imunologia , Proteínas/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa/imunologia , Humanos , Inflamação/imunologiaRESUMO
Mass vaccination of the global population against SARS-CoV-2 will, we hope, turn the tide against this devastating pandemic. To complement vaccinations, better tools are needed to enable viral infections and immunological protection to be monitored. Accurate tools provide sound data for informed decision-making at many levels, from personal to governmental. The measurement of viral RNA is currently routinely used to detect active infections, but only gives a positive result during infection and is unable to reveal historic infections. Tests involving a detection of SARS-CoV-2-specific antibodies can reveal prior exposures to virus and can measure anti-viral immune responses induced after natural infection or after vaccination. They may eventually also be used to predict an individual's likelihood of becoming re-infected. Here, we report on the development of a sensitive ELISA technique to detect multiple isotypes of antibodies against the spike glycoprotein, in samples of both serum and saliva. This paper provides an important step towards understanding the immune response to SARS-CoV-2 and may therefore eventually help us to effectively control it.