RESUMEN
Toll-like receptors (TLRs) play an important role in inducing innate and acquired immune responses against infection. However, the effect of Toll-like receptor 7 (TLR7) on follicular helper T (Tfh) cells in mice infected with Plasmodium is still not clear. The results showed that the splenic CD4+ CXCR5+ PD-1+ Tfh cells were accumulated after Plasmodium yoelii NSM infection, the content of splenic Tfh cells was correlated to parasitemia and/or the red blood cells (RBCs) counts in the blood. Moreover, the expression of TLR7 was found higher than TLR2, TLR3 and TLR4 in splenic Tfh cells of the WT mice. TLR7 agonist R848 and the lysate of red blood cells of infected mice (iRBCs) could induce the activation and differentiation of splenic Tfh cells. Knockout of TLR7 leads to a decrease in the proportion of Tfh cells, down-regulated expression of functional molecules CD40L, IFN-γ, IL-21 and IL-10 in Tfh cells; decreased the proportion of plasma cells and antibody production and reduces the expression of STAT3 and Ikzf2 in Tfh cells. Administration of R848 could inhibit parasitemia, enhance splenic Tfh cell activation and increase STAT3 and Ikzf2 expression in Tfh cells. In summary, this study shows that TLR7 could regulate the function of Tfh cells, affecting the immune response in the spleen of Plasmodium yoelii NSM-infected mice.
Asunto(s)
Malaria , Plasmodium yoelii , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Parasitemia/metabolismo , Plasmodium yoelii/metabolismo , Células T Auxiliares Foliculares/metabolismo , Linfocitos T Colaboradores-Inductores , Receptor Toll-Like 7/metabolismoRESUMEN
Introduction of a fluorine-containing block into block copolymers is an effective method to tune block copolymer nanoassemblies with a microphase-separated structure. However, this microphase-separated structure is difficult to clearly observe due to its nanoscale size. In this work, fluorine-containing ABC triblock copolymer vesicles of poly(ethylene glycol)-block-polystyrene-block-poly(4-vinylbenzyl pentafluorophenyl ether) (PEG-b-PS-b-PVBFP) are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization under dispersed condition. Owing to the choice of a suitable degree of polymerization of the three blocks, the synthesized PEG45-b-PS197-b-PVBFP233 vesicles have a relatively large size of around 216 nm and a thin vesicular membrane with a thickness of around 28 nm. Ascribed to the relatively large size of the vesicles and the thin vesicular membrane, it is concluded that the fluorine-containing PVBFP block forms 9 nm columnar microdomains shielded by the PS phase in the vesicular membrane.
RESUMEN
CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103+ T cells are not thoroughly elucidated in the liver of mouse infected with Plasmodium. Six- to eight-week-old C57BL/6 mice were infected with Plasmodium yoelii nigeriensis NSM. Mice were sacrificed on 12-16 days after infection and the livers were picked out. Sections of the livers were stained, and serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103+CD8+ Tc cell were analyzed by using flow cytometry, respectively. Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. Only CD8+ Tc and γδT cells expressed higher levels of CD103 in the uninfected state.CD103 expression in CD8+ Tc cells significantly decreased after infection. Compared to that of CD103- CD8+ Tc cells, CD103+ CD8+ Tc cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. CD103+CD8+ Tc cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium yoelii nigeriensis NSM infection.
Asunto(s)
Malaria , Plasmodium yoelii , Animales , Ratones , Linfocitos T CD8-positivos/metabolismo , Interleucina-10/metabolismo , Interleucina-17 , Interleucina-4 , Hígado , Malaria/inmunología , Malaria/metabolismo , Ratones Endogámicos C57BLRESUMEN
A systematic review was conducted on the literature on feeding behaviors in Chinese families of children under 6 years old. Forty relevant publications were identified, of which 33 were published in Chinese, 7 in English. All studies were questionnaire-based and used a cross-sectional research design. Approximately half of the studies reported a score for each feeding practice/style, based on a Likert scale; the other half dichotomized these scores into a percentage of the population that reported frequent use of the behaviors. The most commonly reported feeding style of Chinese caregivers was a locally defined "active response" style that somewhat resembled authoritative parenting. The most commonly reported feeding practices were praise, encouraging trying new foods, encouragement of balanced diet and encouragement of healthy eating. Some behaviors showed a great deal of variance in prevalence between studies, which may be at least partially due to differences in methodology and how behaviors were defined. Some feeding behaviors varied in frequency depending on the child's age, although longitudinal studies are needed to better understand how these evolve over time. Child body composition was also associated with feeding behaviors use, although the direction of the association cannot be determined due to the cross-sectional nature of the research. There is still an important gap in the literature regarding the feeding behaviors of non-maternal caregivers, as grandparents often play an important role in childcare in China.
Asunto(s)
Conducta Alimentaria , Responsabilidad Parental , Pueblo Asiatico , Niño , Preescolar , Estudios Transversales , Humanos , Lactante , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To explore the genetic basis for a child presented with renal failure and multi-cystic dysplastic kidney without anal atresia. METHODS: Peripheral blood sample of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The 40-day-old infant had presented with vomiting brown matter in a 7 days neonate and was transferred for kidney failure. Clinical examination has discovered renal failure, polycystic renal dysplasia, congenital hypothyroidism, bilateral thumb polydactyly, sensorineural hearing loss and preauricular dermatophyte. Genetic testing revealed that he has harbored a previously unreported c.824delT, p.L275Yfs*10 frameshift variant of SALL1 gene, which was confirmed by Sanger sequencing as de novo. CONCLUSION: The patient was diagnosed with Townes-Brocks syndrome due to the novel de novo variant of SALL1 gene. Townes-Brocks syndrome without anal atresia is rare. Above finding has also enriched the mutational spectrum of the SALL1 gene.
Asunto(s)
Ano Imperforado , Pérdida Auditiva Sensorineural , Insuficiencia Renal , Anomalías Múltiples , Ano Imperforado/diagnóstico , Ano Imperforado/genética , Niño , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Humanos , Lactante , Recién Nacido , Masculino , Pulgar/anomalías , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites. METHODS: Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. RESULTS: The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4+, IL-5+, IL-6+, IL-21+, IL-1α+, and IL-17+ γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3+ cells and absolute numbers of CD3+ cells, CD3+ CD4+ cells, CD3+ CD8+ cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3+ and CD3+ CD8+ cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69+, ICOS+, and CD80+ B cells between the WT infected and γδT KO infected mice (p > 0.05). CONCLUSIONS: The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.
Asunto(s)
Linfocitos Intraepiteliales/inmunología , Pulmón/inmunología , Malaria/inmunología , Plasmodium yoelii/fisiología , Animales , Linfocitos B/inmunología , Femenino , Citometría de Flujo , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunologíaRESUMEN
Plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. Although a number of studies have reported the emergence of drug resistance in different therapies for P. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. This research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. Relevant original randomized control trials (RCTs) were searched in all available electronic databases. Pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were used to evaluate the risk of drug resistance resulting from different treatments. Seventy-eight studies were included in the meta-analysis to compare drug resistance in the treatment of P. falciparum infections and yielded the following results: chloroquine (CQ) > sulfadoxine-pyrimethamine (SP) (RR = 3.67, p < 0.001 ), mefloquine (MQ) < SP (RR = 0.26, p < 0.001), artesunate + sulfadoxine-pyrimethamine (AS + SP) > artemether + lumefantrine (AL) (RR = 2.94, p < 0.001), dihydroartemisinin + piperaquine (DHA + PQ) < AL (RR = 0.7, p < 0.05), and non-artemisinin-based combination therapies (NACTs) > artemisinin-based combination therapies (ACTs) (RR = 1.93, p < 0.001); no significant difference was found in amodiaquine (AQ) vs. SP, AS + AQ vs. AS + SP, AS + AQ vs. AL, or AS + MQ vs. AL. These results presented a global view for the current status of antimalarial drug resistance and provided a guidance for choice of antimalarials for efficient treatment and prolonging the life span of the current effective antimalarial drugs.
Asunto(s)
Antimaláricos/uso terapéutico , Resistencia a Medicamentos , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Amodiaquina/uso terapéutico , Artemisininas/uso terapéutico , Cloroquina/uso terapéutico , Combinación de Medicamentos , Quimioterapia Combinada , Humanos , Malaria Falciparum/parasitología , Mefloquina/uso terapéutico , Pirimetamina/uso terapéutico , Quinolinas/uso terapéutico , Riesgo , Sulfadoxina/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: In arid environments, a high nitrogen content per leaf area (Narea) induced by drought can enhance water use efficiency (WUE) of photosynthesis, but may also lead to high leaf construction cost (CC). Our aim was to investigate how maximizing Narea could balance WUE and CC in an arid-adapted, widespread species along a rainfall gradient, and how such a process may be related to the drought threshold of the desert-steppe ecotone in northern China. METHODS: Along rainfall gradients with a moisture index (MI) of 0·17-0·41 in northern China and the northern Tibetan Plateau, we measured leaf traits and stand variables including speciï¬c leaf area (SLA), nitrogen content relative to leaf mass and area (Nmass, Narea) and construction cost (CCmass, CCarea), δ(13)C (indicator of WUE), leaf area index (LAI) and foliage N-pool across populations of Artemisia ordosica KEY RESULTS: In samples from northern China, a continuous increase of Narea with decreasing MI was achieved by a higher Nmass and constant SLA (reduced LAI and constant N-pool) in high-rainfall areas (MI > 0·29), but by a lower SLA and Nmass (reduced LAI and N-pool) in low-rainfall areas (MI ≤ 0·29). While δ(13)C, CCmass and CCarea continuously increased with decreasing MI, the low-rainfall group had higher Narea and δ(13)C at a given CCarea, compared with the high-rainfall group. Similar patterns were also found in additional data for the same species in the northern Tibetan Plateau. The observed drought threshold where MI = 0·29 corresponded well to the zonal boundary between typical and desert steppes in northern China. CONCLUSIONS: Our data indicated that below a climatic drought threshold, drought-resistant plants tend to maximize their intrinsic WUE through increased Narea at a given CCarea, which suggests a linkage between leaf functional traits and arid vegetation zonation.
Asunto(s)
Artemisia/fisiología , Nitrógeno/metabolismo , Fotosíntesis/fisiología , Agua/fisiología , China , Sequías , Ambiente , Hojas de la Planta/fisiologíaRESUMEN
Objective: To examine the secretion and localization of Toxoplasma gondii Rhoptry protein 16 ï¼ROP16ï¼ during invasion of different strains of T. gondii into host cells. Methods: The Tgrop16 gene was amplified by PCR on the cDNA of T. gondii RH strain, subcloned into the plasmid pET-32aï¼+ï¼, and expressed in Escherichia coli BL21ï¼DE3ï¼ under the induction of isopropyl ß-D-1-thiogalactopyranoside. New Zealand rabbit was immuned with the expressed recombinant protein TgROP16 to produce polyclonal anti-TgROP16 antibody. The specificity and sensitivity of the polyclonal antibody were examined by Western blotting and indirect ELISA, respectively. The transcriptional and protein levels of Tgrop16 in T. gondii RH strain and Pru strain were determined by real-time PCR and Western blotting, respectively. The secretion and distribution of TgROP16 in human foreskin fibroblasts (HFFs) during the invasion by T. gondii RH strain and Pru strain were examined by indirect immunofluorescence assay (IFA). Results: Western blotting showed a specific band at M(r) of ï½100 000, indicating that the specific rabbit-derived anti-TgROP16 polyclonal antibody was capable of recognizing TgROP16. Indirect ELISA revealed a titer of 1:25 600 for the antibody. The relative expression level of Tgrop16 in Pru strainï¼»ï¼7.786±0.206ï¼ï¼½ was 7 times than that in RH strainï¼»ï¼1.000±0.110ï¼ï¼½ï¼P<0.05ï¼ as detected by real-time PCR, and TgROP16 protein level was higher in RH strain than in Pru strain. IFA showed that TgROP16 was localized on the apical complex of the unrecruited tachyzoite of T. gondii before invasion and was secreted out of the recruited tachyzoite after invasion. Conclusion: The anti-TgROP16 polyclonal antibody has high specificity and sensitivity. The TgROP16 protein level is higher in the RH strain than in the Pru strain. For both strains, TgROP16 is localized on the apical complex of the unrecruited tachyzoite before invasion and secreted out of the recruited tachyzoite during invasion.
Asunto(s)
Toxoplasma , Animales , Anticuerpos , Western Blotting , ADN Complementario , Ensayo de Inmunoadsorción Enzimática , Humanos , Plásmidos , Reacción en Cadena de la Polimerasa , Proteínas Tirosina Quinasas , Proteínas Protozoarias , ConejosRESUMEN
Small intestine samples of neonatal cat were aseptically collected from the jejunum-ileum region and digested with collagenase XI/dispase I. Immunohistochemistry results showed that feline intestinal epithelial cells were successfully isolated and could be cultured. Cytokeratin was positive in the cytoplasm of feline intestinal epithelial cells. The cells were infected with the bradyzoites of Toxoplasma gondii Prugniaud strain, and the rupture of the cells was observed on the 72nd day post-infection. The sexual stage of T. gondii did not occur, however.
Asunto(s)
Células Epiteliales/parasitología , Intestino Delgado/citología , Toxoplasma , Toxoplasmosis Animal , Animales , Gatos , Células Cultivadas , InmunohistoquímicaRESUMEN
OBJECTIVE: To prepare and purify polyclonal antibody against Toxoplasma gondii rhoptry protein 2 (ROP2) and apply it to immunofluorescence localization. METHODS: The constructed recombinant plasmid pET32a-ROP2 was transformed into E. coli BL21 (DE3) and the protein was expressed under the condition of 0.5 mmol/L IPTG induction. Cells were lysed by multiple rounds of sonication to obtain supernatant and inclusion body, respectively. The washed inclusion bodies were dissolved in urea. New Zealand White rabbits were immunized with 200 microg purified recombinant ROP2 mixing with the same volume of Freund's adjuvant for 3 times at interval of 14 days and 19 days, respectively. Rabbit serum was collected at 10 days after the last immunization. Polyclonal antibody in rabbit serum was purified with HiTrap Protein G HP affinity purification column. Indirect ELISA and Western blotting were used to detect antibody titer and specificity of polyclonal antibody against the recombinant ROP2. The polyclonal antibody was used to the localization of ROP2 on the parasitophorous vacuole membrane in human foreskin fibroblasts infected by Toxoplasma tachyzoites by the immunofluorescence method. RESULTS: The recombinant ROP2 protein was obtained and specific rabbit-derived polyclonal antibody was prepared. Indirect ELISA confirmed that the rabbit-derived polyclonal antibody titer reached 1:102400, and the recombinant ROP2 protein was recognized by specific polyclonal antibody. Immunofluorescence localization test showed that the ROP2 protein was located on the parasitophorous vacuole membrane. CONCLUSION: The rabbit-derived polyclonal antibody against ROP2 is prepared, and used in immunofluorescence localization of ROP2 on parasitophorous vacuole membrane.
Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Proteínas de la Membrana/aislamiento & purificación , Proteínas Protozoarias/aislamiento & purificación , Toxoplasma/química , Animales , Western Blotting , Escherichia coli , Técnica del Anticuerpo Fluorescente , Humanos , Inmunización , Proteínas de la Membrana/inmunología , Plásmidos , Proteínas Protozoarias/inmunología , Conejos , Proteínas RecombinantesRESUMEN
BACKGROUND: The incidence of composite endpoint of early safety (CEES) after transcatheter aortic valve replacement (TAVR) has been a topic of focus within the cardiovascular field due to its impact on long-term patient outcomes. Timely prophylactic interventions are crucial for patients identified as high risk for CEES through preoperative risk stratification. OBJECTIVES: This study aimed to explore the connection between inflammatory and nutritional markers, specifically the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), and CEES occurrence. MATERIAL AND METHODS: A cohort of 134 patients undergoing TAVR in a single center was studied. The study endpoint was the occurrence of CEES, which was defined according to the Valve Academic Research Consortium 3. RESULTS: The CEES was reached in 25.4% of patients at 30 days. A high NLR was associated with a 5.55-fold increased risk of CEES (95% confidence interval (95% CI): 1.52-20.29; p < 0.05), while a low PNI was linked to a 4.43-fold increased risk (95% CI: 1.55-12.65; p < 0.01). Combining NLR and PNI provided additional risk stratification for high-risk patients (hazard ratio (HR), 95% CI: 2.24-43.37; p < 0.005). CONCLUSIONS: A high NLR and low PNI were shown to be significant predictors of CEES following TAVR. These findings underscore the significance of NLR and PNI in the risk assessment of TAVR patients, offering valuable insights for preventive measures.
RESUMEN
AIM: To analyze the sequencing results of circular RNAs (circRNAs) in cardiomyocytes between the doxorubicin (DOX)-injured group and exosomes treatment group. Moreover, to offer potential circRNAs possibly secreted by exosomes mediating the therapeutic effect on DOX-induced cardiotoxicity for further study. METHODS: The DOX-injured group (DOX group) of cardiomyocytes was treated with DOX, while an exosomes-treated group of injured cardiomyocytes were cocultured with bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BEC group). The high-throughput sequencing of circRNAs was conducted after the extraction of RNA from cardiomyocytes. The differential expression of circRNA was analyzed after identifying the number, expression, and conservative of circRNAs. Then, the target genes of differentially expressed circRNAs were predicted based on the targetscan and Miranda database. Next, the GO and KEGG enrichment analyses of target genes of circRNAs were performed. The crucial signaling pathways participating in the therapeutic process were identified. Finally, a real-time quantitative polymerase chain reaction experiment was conducted to verify the results obtained by sequencing. RESULTS: Thirty-two circRNAs are differentially expressed between the two groups, of which twenty-three circRNAs were elevated in the exosomes-treated group (BEC group). The GO analysis shows that target genes of differentially expressed circRNAs are mainly enriched in the intracellular signalactivity, regulation of nucleic acid-templated transcription, Golgi-related activity, and GTPase activator activity. The KEGG analysis displays that they were involved in the autophagy biological process and NOD-like receptor signaling pathway. The verification experiment suggested that mmu_circ_0000425 (ID: 116324210) was both decreased in the DOX group and elevated in BEC group, which was consistent with the result of sequencing. CONCLUSION: mmu_circ_0000425 in exosomes derived from bone marrow mesenchymal stem cells (BMSC) may have a therapeutic role in alleviating doxorubicin-induced cardiotoxicity (DIC).
Asunto(s)
Doxorrubicina , Exosomas , Células Madre Mesenquimatosas , Miocitos Cardíacos , ARN Circular , ARN Circular/genética , ARN Circular/metabolismo , Doxorrubicina/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Exosomas/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Animales , Perfilación de la Expresión Génica , Ratas , Células CultivadasRESUMEN
IMPORTANCE: This is the first report that a human E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (Cbl-b), functions as a host dependency factor for the intracellular protozoan Toxoplasma gondii and the mechanism for how T. gondii infection inhibits the TLR/MyD88 innate immunity pathway through MyD88 degradation mediated by Cbl-b. This finding is an impactful contribution for understanding the host cell immunity against T. gondii infection.
Asunto(s)
Factor 88 de Diferenciación Mieloide , Toxoplasma , Humanos , Inmunidad Innata , Ubiquitina-Proteína LigasasRESUMEN
Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8+ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8+ and TIGIT+CD8+ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT+CD8+ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT+CD8+T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8+ and TIGIT+CD8+ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT+CD8+ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT+CD8+ T cells from the normal mice. The percentages of TIGIT+CD8+ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT+CD8+ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
Asunto(s)
Malaria , Plasmodium yoelii , Animales , Ratones , Linfocitos T CD8-positivos , Citocinas/metabolismo , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Pulmón/metabolismo , Malaria/metabolismo , Plasmodium yoelii/metabolismo , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7 -/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7 -/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7.
Asunto(s)
Malaria , Bazo , Ratones , Animales , Bazo/metabolismo , Eritropoyesis , Receptor Toll-Like 7 , Ratones Endogámicos C57BL , Interferón gamma/uso terapéutico , Macrófagos/metabolismo , Hierro/metabolismoRESUMEN
Toll-like receptors (TLRs) play an important role in the induction of innate and adaptive immune responses against Schistosoma japonicum (S. japonicum) infection. However, the role of Toll-like receptor 7 (TLR7) in the mouse lung during S. japonicum infection and the myeloid-derived suppressor cells (MDSCs) affected by the absence of TLR7 are not clearly understood. In this study, the results indicated that the MDSCs were accumulated and the proportion and activation of CD4+ and CD8+ T cells were decreased in the lung of mice at 6-7 weeks after S. japonicum infection. Then, the expression of TLR7 was detected in isolated pulmonary MDSCs and the results showed that the expression of TLR7 in MDSCs was increased after infection. Furthermore, TLR7 agonist R848 could down-regulate the induction effect of the soluble egg antigen (SEA) on pulmonary MDSCs in vitro. Meanwhile, TLR7 deficiency could promote the pulmonary MDSCs expansion and function by up-regulating the expression of PD-L1/2 and secreting of IL-10 in the mice infected with S. japonicum. Mechanistic studies revealed that S. japonicum infection and the antigen effects are mediated by NF-κB signaling. Moreover, TLR7 deficiency aggravates S. japonicum infection-induced damage in the lung, with more inflammatory cells infiltration, interstitial dilatation and granuloma in the tissue. In summary, this study indicated that TLR7 signaling inhibits the accumulation and function of MDSCs in S. japonicum infected mouse lung by down-regulating the expression of PD-L1/2 and secreting of IL-10, via NF-κB signaling.
Asunto(s)
Células Supresoras de Origen Mieloide , Esquistosomiasis Japónica , Receptor Toll-Like 7 , Animales , Ratones , Antígeno B7-H1/metabolismo , Interleucina-10/metabolismo , Pulmón , Ratones Endogámicos C57BL , Células Supresoras de Origen Mieloide/metabolismo , FN-kappa B , Schistosoma japonicum/fisiología , Esquistosomiasis Japónica/inmunología , Receptor Toll-Like 7/metabolismoRESUMEN
The morbidity and mortality of malaria are still high. Programmed cell death-1(PD-1) is an important co-inhibitory factor and CD8 T cells with PD-1 were reported to be exhausted cells. It remains unknown what the role of CD4 T cells expressing PD-1 is and what the upstream regulating molecules of PD-1 in CD4 T cells are. The C57BL/6 mice were injected with Plasmodium yoelii (P. yoelii) in this study. Expressions of PD-1, activation markers, and cytokines were tested. The differentially expressed genes between PD-1+/- CD4 T cells were detected by microarray sequencing. Western blot, chromatin immunoprecipitation (ChIP), siRNA, hypoxia inducible factor-1α (HIF-1α) inducer and inhibitor were used to explore PD-1's upstream molecules, respectively. The proportions of PD-1+ CD4 T cells increased post P. yoelii infection. PD-1+ CD4 T cells expressed more activated surface markers and could produce more cytokines. Nuclear factor of activated T cells 1 (NFATc1) was found to be a key transcription factor to induce PD-1 expression after infection. Both the inducer and the inhibitor of HIF-1α could change the expressions of NFATc1 and PD-1 in vivo and in vitro, respectively. Taken together, P. yoelii infection induced NFATc1 expression by HIF-1α. The highly expressed NFATc1 entered the nucleus and initiated PD-1 expression. PD-1+ CD4 T cells appeared to be more activated and could secrete more cytokines to regulate the host's immune responses against malaria.
Asunto(s)
Linfocitos T CD4-Positivos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Malaria , Factores de Transcripción NFATC , Plasmodium yoelii , Receptor de Muerte Celular Programada 1 , Animales , Linfocitos T CD4-Positivos/inmunología , Citocinas/inmunología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/inmunología , Malaria/genética , Malaria/inmunología , Malaria/parasitología , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/inmunología , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Transducción de SeñalRESUMEN
High glucose metabolism is recognized as one of the hallmarks of cancer and increased expression levels of several key factors involved in glucose metabolism have been reported in non-small cell lung cancer (NSCLC). Previous studies showed that microRNA (miR)-218 is reduced in NSCLC, but its function in glucose metabolism in NSCLC is not fully understood. The present study aimed to investigate the effect of miR-218 on glucose metabolism in NSCLC cell lines and the underlying molecular mechanism. The present results suggested that miR-218 reduced glucose consumption, the mechanism of glycolysis and activity in the pentose phosphate pathway. In addition, glucose transporter 1 (GLUT1) was identified to be a direct target of miR-218, while overexpression of GLUT1 did not abolish the effect of miR-218 on glucose metabolism. The present results indicated that phosphorylation of NF-κB p65 was significantly decreased by miR-218 in NSCLC cells and that activation of NF-κB led to the inhibition of miR-218 regulation of glucose metabolism. In conclusion, the present results suggested that miR-218 downregulated glucose metabolism in NSCLC not only by directly targeting GLUT1, but also via the NF-κB signaling pathway.
RESUMEN
B cells played an important role in Schistosoma infection-induced diseases. TLR7 is an intracellular member of the innate immune receptor. The role of TLR7 on B cells mediated immune response is still unclear. Here, C57BL/6 mice were percutaneously infected by S. japonicum for 5-6 weeks. The percentages and numbers of B cells increased in the infected mice (p < 0.05), and many activation and function associated molecules were also changed on B cells. More splenic cells of the infected mice expressed TLR7, and B cells were served as the main cell population. Moreover, a lower level of soluble egg antigen (SEA) specific antibody and less activation associated molecules were found on the surface of splenic B cells from S. japonicum infected TLR7 gene knockout (TLR7 KO) mice compared to infected wild type (WT) mice (p < 0.05). Additionally, SEA showed a little higher ability in inducing the activation of B cells from naive WT mice than TLR7 KO mice (p < 0.05). Finally, the effects of TLR7 on B cells are dependent on the activation of NF-κB p65. Altogether, TLR7 was found modulating the splenic B cell responses in S. japonicum infected C57BL/6 mice.