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1.
Langmuir ; 35(34): 11108-11113, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31364855

RESUMO

It is easy to achieve extremely low friction of graphene or graphite in dry conditions via the formation of an incommensurate interface but is difficult to achieve with water lubrication. Herein, we propose a new strategy to achieve extremely low friction on a graphitic surface in water by self-assembling cationic surfactant micelles in the contact zone. When uniform surfactant micelles are formed on silica and freshly cleaved graphene layers via self-assembly under low contact pressure, the friction coefficient between them can reduce to 0.0004. When the self-assembled micelles are ruptured in the contact zone by high pressure, the friction coefficient between them would increase to 0.005 (still in the superlubricity regime). The mechanism of the different friction behaviors was studied at the nanoscale, which was attributed to the formation of different shear planes that shifts from the interface of the micelle/micelle to surfactant molecules/graphene layers after micellar rupture. The results provide direct evidence that the cationic surfactant micelles can efficiently lubricate graphitic surface regardless of micellar rupture.

2.
ACS Appl Mater Interfaces ; 11(35): 32569-32576, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31414588

RESUMO

Newly emerging two-dimensional (2D) materials of MXenes possess lots of merits, which provide potential solutions for the lubrication issues in harsh conditions. Here, preliminary efforts were devoted to developing an MXene-based 2D composite coating and its antiwear interfacial performance in ambient environments. Macroscale and atomic-scale characterizations were utilized to explore the lubrication behaviors of the composite coating to clarify the influence of the coating composition and tribo-test parameters in the establishment of ultra-wear-resistant sliding interfaces. The results highlighted a unique lubrication mechanism for the 2D MXene composite coating. They suggested that the MXene/nanodiamond coating exhibited almost no wear when rubbed against a polytetrafluoroethylene (PTFE) ball. A nanostructured tribofilm with unprecedented bonding features was in situ formed along the sliding interface. The ultra-wear resistance highly depended on the combined effects of shielding and self-lubrication of PTFE, layer shearing of MXenes, and self-rolling of nanodiamond. These discoveries clearly enrich the 2D material-based lubrication theories and offer technical guidance for designing and exploiting high-performance ultra-wear-resistant materials.

3.
MBio ; 10(4)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455656

RESUMO

Recruitment of monocytes to the infection site is critical for host resistance against Mycobacterium tuberculosis CD157 has a crucial role in neutrophil and monocyte transendothelial migration and adhesion, but its role in tuberculosis (TB) is unclear. Here, we show that both mRNA and protein levels of Cd157 are significantly increased during M. tuberculosis infection. Deficiency of Cd157 impaired host response to M. tuberculosis infection by increasing bacterial burden and inflammation in the lung in the murine TB model. In vitro experiments show that the bactericidal ability was compromised in Cd157 knockout (KO) macrophages, which was due to impaired M. tuberculosis-induced reactive oxygen species (ROS) production. We further reveal that CD157 interacts with TLR2 and PKCzeta and facilitates M. tuberculosis-induced ROS production in Cd157 KO macrophages, which resulted in enhanced M. tuberculosis killing. For the clinic aspect, we observe that the expression of CD157 decreases after effective anti-TB chemotherapy. CD157 is specifically increased in pleural fluid in tuberculous pleurisy patients compared to pneumonia and lung cancer patients. Interestingly, the levels of soluble CD157 (sCD157) correlate with human peripheral monocyte-derived macrophage bactericidal activity. Exogenous application of sCD157 could compensate for macrophage bactericidal ability and restore ROS production. In conclusion, we have identified a novel protective immune function of CD157 during M. tuberculosis infection via TLR2-dependent ROS production. Application of sCD157 might be an effective strategy for host-directed therapy against TB in those with insufficient CD157 production.IMPORTANCE Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis, remains a major global health problem. CD157, a dual-function receptor and ß-NAD+-metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro, which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis-induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.

4.
ACS Appl Mater Interfaces ; 11(28): 25535-25546, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31264826

RESUMO

Onion-like carbon (OLC), spherical nanoparticles consisting of carbon shells, is capable of providing exceptional lubrication effects. Nevertheless, the underlying mechanism, especially the tribo-induced evolution of interfacial nanostructures and their correlation with the friction states, is not clear. In this work, OLC films with a thickness of ∼1 µm were synthesized by electrophoretic deposition on the mirror-polished stainless steel. The lubricity was evaluated by tailoring the sliding aspects including applied normal load, contact time, and counterface materials. It is found that the friction reduction level is highly dependent on the material transfer and transformation of the OLC surface and the physicochemical nature of the as-formed tribolayer in the contact areas. The subsurface of the OLC film always undergoes a deep amorphization transformation upon sliding. It is interesting to note that the tribolayer formed on the bare steel ball is mainly composed of highly ordered graphene-like nanoflakes derived from the sliding-induced degradation of OLC nanospheres. In comparison, the nanospherical carbon structure can be retained in the topmost subsurface of the tribolayer formed on the ceramic Si3N4 ball. Such a nanosphere-/amorphization-coupled interface is capable of providing a robust lubrication state under high contact stresses. The findings identify a new lubrication mechanism for the spherical carbon nanostructure, rendering them effective solid lubricants.

5.
World J Gastroenterol ; 25(20): 2473-2488, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31171891

RESUMO

BACKGROUND: It is challenging to distinguish intestinal tuberculosis from Crohn's disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn's disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1ß rs1143627, TGFß rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

6.
Rev Invest Clin ; 71(3): 204-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184336

RESUMO

Background: Osteoporosis (OP) is common in patients with chronic obstructive pulmonary disease (COPD). The relationship between OP and COPD has been primarily studied in male patients, and few reports are available in postmenopausal women. Objective: The purpose of this study was to investigate the association between bone mineral density (BMD) and COPD in postmenopausal women. Methods: This cross-sectional study included 133 clinically stable female ex-smokers with confirmed COPD, and 31 age-matched "ex-smoker" female controls. We analyzed groups according to their airway obstruction category. BMD was measured on dual-energy X-ray absorptiometry images of the left femoral neck. Results: Patients with COPD had lower T-scores and higher prevalence of osteopenia/OP than the control group. In the COPD group, the airway obstruction category was significantly associated with the T-score after adjustment for confounders. Multivariate logistic regression analysis showed COPD was an independent marker for increased risk of osteopenia/OP in postmenopausal women. Conclusions: COPD and airway obstruction category were strongly related to BMD. Postmenopausal women with COPD, especially those with severe airway obstruction, had a higher prevalence rate and a higher risk of osteopenia and OP than female controls without COPD.

7.
Mol Immunol ; 112: 175-181, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170628

RESUMO

Regulatory B cells (Bregs) have critical roles as a negative regulator of immunity, mainly due to the fact that it secrets high a level of interleukin 10 (IL-10). Recently, a new subset of Bregs was identified as a key source of IL-35, which is an immunosuppressive cytokine and conventionally thought to be secreted by regulatory T cells (Tregs). Our previous study showed that the level of IL-35 in serum was elevated in the patients with active tuberculosis (ATB). However, none of the studies reported that IL-35 is secreted by B cells in ATB patients. In the current study, we found that the mRNA expressions of the both subunits (p35 and Ebi3) of IL-35 by circulating B cells were increased in ATB patients. By using immunohistochemistry and immunofluorescence staining, we found a subset of B cells infiltrated into the tuberculous granuloma of ATB patients also expressed IL-35. Moreover, Mycobacterium tuberculosis (MTB) lysate stimulation assay also demonstrated higher levels of IL-35 were exerted by MTB lysate within purified B cells from healthy control group (HC). Flow cytometry analysis further showed that the IL-35-producing B cells from ATB patients produced a higher level of IL-10. Taken together, IL-35-producing B cells may play a regulatory role during MTB infection by producing IL-10.

8.
J Leukoc Biol ; 106(3): 749-757, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254317

RESUMO

Depression is a major mental health condition and is expected be the most debilitating and widespread health disorder by 2030. Tuberculosis (TB) is also a leading cause of morbidity and mortality worldwide and interestingly, is a common comorbidity of depression. As such, much attention has been paid to the association between these 2 pathologies. Based on clinical reports, the association between TB and depression seems to be bidirectional, with a substantial overlap in symptoms between the 2 conditions. TB infection or reactivation may precipitate depression, likely as a consequence of the host's inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis. Nevertheless, few studies have considered whether patients with depression are at a higher risk for TB. In this review, we discuss the hypotheses on the association between depression and TB, highlighting the immuno-inflammatory response and lipid metabolism as potential mechanisms. Improving our understanding of the interplay between these 2 disorders should help guide TB clinical care and prevention both in patients with comorbid depression and in the general population.

9.
Nat Microbiol ; 4(8): 1378-1388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31110366

RESUMO

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-ß-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.

10.
Biomed Res Int ; 2019: 9537050, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093505

RESUMO

Background: Because of the similarity of intestinal tuberculosis and Crohn's disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn's disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn's disease, and 700 normal controls in this study. Methods: All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. Results: The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn's disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn's patients requiring glucocorticoids (p<0.05). Conclusions: The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn's disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn's disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Doença de Crohn/genética , Epóxido Hidrolases/genética , Grupos Étnicos/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Tuberculose Gastrointestinal/genética , Adulto , Doença de Crohn/enzimologia , Feminino , Frequência do Gene/genética , Humanos , Masculino , Modelos Genéticos , Tuberculose Gastrointestinal/enzimologia
12.
Molecules ; 24(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991677

RESUMO

Four new compounds including two new sesquiterpenoid dimers, commiphoroids E (1) and F (2), a new triterpenoid (3), and a new sesquiterpenoid (4), along with three known terpenoids (5-7) were isolated from Resina Commiphora, whose structures were identified by NMR spectra, HRESIMS, and X-ray diffraction analysis. Compounds 1 and 2 both bear an O-bridge ring and feature a plausible [4 + 2] Diels-Alder cycloaddition reaction. Antimycobacterial activities show that all the tested compounds (200 µM) could inhibit the growth of both sensitive and clinically multi-drug resistant (MDR) isolated strains. In addition, cellular toxicity of the isolates against human cancer cells and THP-1 monocyte cells was examined.


Assuntos
Antituberculosos , Commiphora/química , Mycobacterium tuberculosis/crescimento & desenvolvimento , Resinas Vegetais/química , Terpenos , Antituberculosos/química , Antituberculosos/farmacologia , Humanos , Células THP-1 , Terpenos/química , Terpenos/farmacologia
13.
Sci Rep ; 9(1): 3042, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816178

RESUMO

Tuberculosis (TB) is a continuing major threat to global health and a leading cause of death, particularly in developing countries. In this study, we aimed to identify a specific and sensitive diagnostic biomarker and develop a vaccine to prevent this disease. We investigated membrane proteins to reveal biomarkers in serum and peripheral blood mononuclear cells (PBMCs) obtained from TB patients. We employed Western blotting to evaluate serological immunoglobulin G levels, and Enzyme Linked Immunospot (ELISpot) to assess the antigen-specific cellular interferon-γ secretion from PBMCs after membrane protein stimulation. A total of 219 membrane proteins were identified, 52 exhibited at a higher levels than the 38-kDa prositive control. Of these 18 exhibited reacted ratios above 1, especially Rv1111c (427-981), with a ratios at 3.38. Accuracy and sensitivity were markedly higher for the top two antigen candidates, Rv0232 and Rv1115, after two rounds of ELISpot tests than ESAT-6 in the commercial kit (42.15 and 43.62%, respectively). These two proteins were administered to mice to detect whether they acted as effective antigens in vivo. These data provide a comprehensive view of the membranes involved in humoural and cellular immune responses that may be used as biomarkers for TB and candidates for a vaccine.

14.
Tuberculosis (Edinb) ; 113: 65-75, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30514515

RESUMO

DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BERopt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer+ CD8+ T cells in peripheral blood and IFN-γ-secreting CD8+ T cells in splenocytes. Meanwhile, the BERopt vaccine-induced long-lasting T cell immunity protected BALB/c mice from high dose viral challenge using a modified vaccinia virus Tiantan strain expressing mature Ag85B protein (MVTT-m85B) and the virulent M. tb H37Rv aerosol challenge. Since the BERopt DNA vaccine does not induce anti-vector immunity, the strong immunogenicity and protective efficacy of this novel DNA vaccine warrant its future development for M. tb prevention and immunotherapy to alleviate the global TB burden.

15.
Nature ; 564(7734): E5, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30377311

RESUMO

The spelling of author Qianting Yang was corrected; the affiliation of author Stephanus T. Malherbe was corrected; and graphs in Fig. 4b and c were corrected owing to reanalysis of the data into the correct timed intervals.

16.
Nat Commun ; 9(1): 4072, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30287856

RESUMO

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, Pcombined = 1.72 × 10-11, OR = 1.277, ESRRB) and 20p13 (rs6114027, Pcombined = 2.37 × 10-11, OR = 1.339, TGM6). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6-deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB.

17.
Nature ; 560(7720): 644-648, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30135583

RESUMO

Most infections with Mycobacterium tuberculosis (Mtb) manifest as a clinically asymptomatic, contained state, known as latent tuberculosis infection, that affects approximately one-quarter of the global population1. Although fewer than one in ten individuals eventually progress to active disease2, tuberculosis is a leading cause of death from infectious disease worldwide3. Despite intense efforts, immune factors that influence the infection outcomes remain poorly defined. Here we used integrated analyses of multiple cohorts to identify stage-specific host responses to Mtb infection. First, using high-dimensional mass cytometry analyses and functional assays of a cohort of South African adolescents, we show that latent tuberculosis is associated with enhanced cytotoxic responses, which are mostly mediated by CD16 (also known as FcγRIIIa) and natural killer cells, and continuous inflammation coupled with immune deviations in both T and B cell compartments. Next, using cell-type deconvolution of transcriptomic data from several cohorts of different ages, genetic backgrounds, geographical locations and infection stages, we show that although deviations in peripheral B and T cell compartments generally start at latency, they are heterogeneous across cohorts. However, an increase in the abundance of circulating natural killer cells in tuberculosis latency, with a corresponding decrease during active disease and a return to baseline levels upon clinical cure are features that are common to all cohorts. Furthermore, by analysing three longitudinal cohorts, we find that changes in peripheral levels of natural killer cells can inform disease progression and treatment responses, and inversely correlate with the inflammatory state of the lungs of patients with active tuberculosis. Together, our findings offer crucial insights into the underlying pathophysiology of tuberculosis latency, and identify factors that may influence infection outcomes.

18.
Diagn Microbiol Infect Dis ; 92(3): 245-249, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30076042

RESUMO

Diagnosis of cervical tuberculous lymphadenitis (CTL), the most commonly occurring form of extrapulmonary tuberculosis, remains as a challenge in clinic. Detection of the presence of Mycobacterium tuberculosis (Mtb) in fine needle aspiration cytology (FNAC) samples is one golden criterion to confirm the CTL diagnosis. Due to the non-specific clinical presentation, CTL might be confused with other lymph node enlargement diseases; therefore empirical treatment with non-anti-TB antibiotics is often initially administered. However, it is still unclear whether this diagnostic antibiotic treatment affects the positivity of Mtb detection in FNAC. The demographics and clinical characteristics of 732 lymph node enlargement patients who had underwent FNAC were retrospectively analyzed and 605 (82.65%) of them were diagnosed as CTL. A total of 279 CTL cases (279/605, 46.11%) with completion of three Mtb tests (AFB, NAAT, and Mtb culture) in FNAC samples were selected for analyzing the effect of empirical antibiotic treatment on the positivity of Mtb tests. Compared to CTL patients without antibiotic treatment prior to FNAC, patients received empirical non anti-TB treatment had significantly lower positivity for acid fast bacilli staining (adjusted OR 0.11, 95% CI 0.06-0.21), nucleic acid amplification test (NAAT) (adjusted OR 0.38, 95% CI 0.21-0.71), and Mtb culture (adjusted OR 0.11, 95% CI 0.06-0.19). In conclusion, this study demonstrated that empirical non anti-TB antibiotic treatment reduced the opportunity to confirm CTL by microbiological analysis. Patients with cervical lymph node enlargement should undergo FNAC for Mtb tests prior to initiation of empirical non anti-TB treatment.

19.
J Infect ; 2018 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-30107196

RESUMO

BACKGROUND: An improved understanding of the gut microbiota could lead to better strategies for the diagnosis, therapy and prophylaxis of tuberculosis (TB). The impact of both Mycobacterium tuberculosis (Mtb) infection and anti-TB treatment on the gut microbiota has rarely been studied. METHODS: We characterized the diversity and composition of the gut microbiota in pulmonary TB patients as well as the effects of anti-TB drugs on the gut microbiota. RESULTS: Pulmonary Mtb infection led to a minor decrease in the α diversity of the gut microbiota when compared to healthy controls, which mainly resulted from changes in the relative abundance of the members of genus Bacteroides. Anti-TB therapy caused a rapid, significant alteration in the community structure. The relative abundance of members of genus Clostridiales of the phylum Firmicutes significantly decreased during anti-TB treatment, while many members of genus Bacteroides, including Bacteroides OTU230 and Bacteroides fragilis, were among the taxa that increased. OTU8 and OTU2972 assigned to family Erysipelotrichaceae of the phylum Firmicutes showed a dramatic increase 1 week after the start of therapy, while the other members of this family decreased. CONCLUSIONS: Pulmonary TB and anti-TB treatment caused a distinct dysbiosis of the gut microbiota. Our study contributes valuable information implying potential links between the gut microbiota and TB.

20.
Cell Rep ; 23(6): 1754-1766, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29742431

RESUMO

T cells are strongly regulated by oxidizing environments and amino acid restriction. How T cells reprogram metabolism to adapt to these extracellular stress situations is not well understood. Here, we show that oxidizing environments and amino acid starvation induce ATF4 in CD4+ T cells. We also demonstrate that Atf4-deficient CD4+ T cells have defects in redox homeostasis, proliferation, differentiation, and cytokine production. We further reveal that ATF4 regulates a coordinated gene network that drives amino acid intake, mTORC1 activation, protein translation, and an anabolic program for de novo synthesis of amino acids and glutathione. ATF4 also promotes catabolic glycolysis and glutaminolysis and oxidative phosphorylation and thereby provides precursors and energy for anabolic pathways. ATF4-deficient mice mount reduced Th1 but elevated Th17 immune responses and develop more severe experimental allergic encephalomyelitis (EAE). Our study demonstrates that ATF4 is critical for CD4+ T cell-mediated immune responses through driving metabolic adaptation.

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