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3.
Cancer Immunol Immunother ; 68(10): 1605-1619, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31531696

RESUMO

The main effectors in tumor control are the class I MHC molecule-restricted CD8+ cytotoxic T lymphocytes (CTLs). Tumor-specific CTL induction can be regulated by dendritic cells (DCs) expressing both tumor-derived epitopes and co-stimulatory molecules. Immunosuppressive tolerogenic DCs, having down-regulated co-stimulatory molecules, are seen within the tumor mass and can suppress tumor-specific CTL induction. The tolerogenic DCs expressing down-regulated XCR1+CD141+ appear to be induced by tumor-derived soluble factors or dexamethasone, while the immunogenic DCs usually express XCR1+CD141+ molecules with a cross-presentation function in humans. Thus, if tolerogenic DCs can be reactivated into immunogenic DCs with sufficient co-stimulatory molecules, tumor-specific CD8+ CTLs can be primed and activated in vivo. In the present study, we converted human tolerogenic CD141+ DCs with enhanced co-stimulatory molecule expression of CD40, CD80, and CD86 through stimulation with non-toxic mycobacterial lipids such as mycolic acid (MA) and lipoarabinomannan (LAM), which synergistically enhanced both co-stimulatory molecule expression and interleukin (IL)-12 secretion by XCR1+CD141+ DCs. Moreover, MA and LAM-stimulated DCs captured tumor antigens and presented tumor epitope(s) in association with class I MHCs and sufficient upregulated co-stimulatory molecules to prime naïve CD3+ T cells to become CD8+ tumor-specific CTLs. Repeat CD141+ DC stimulation with MA and LAM augmented the secretion of IL-12. These findings provide us a new method for altering the tumor environment by converting tolerogenic DCs to immunogenic DCs with MA and LAM from Mycobacterium tuberculosis.


Assuntos
Células Dendríticas/imunologia , Lipopolissacarídeos/farmacologia , Mycobacterium/química , Ácidos Micólicos/farmacologia , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos de Superfície/análise , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Humanos , Interleucina-12/biossíntese , Mycobacterium bovis
4.
Ann Agric Environ Med ; 26(3): 396-399, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31559792

RESUMO

INTRODUCTION AND OBJECTIVE: Bovine tuberculosis (bTB, bovine TB) is caused by mycobacteria which are grouped within the MTBC. TB in animals is a highly infectious and progressive disease which can be transmitted to humans. Since 2009, Poland has gained official bTB-free status. Despite the official fact of bTB-free status, a dozen bTB outbreaks are still noted each year. Since 2000 in Poland, every year 1/5 of the national herd is subject to intradermal skin TB testing to control the bTB outbreaks in the cattle population. Application, with 5-year intervals between each government-funded skin test, undoubtedly resulted in financial savings. However it also seems to have caused several adverse and worrying events, e.g. an increase in the number of reactors detected and removed from a single tested herd. The objective of this study was the examination of 898 cattle imputed with bTB infection in Poland between 2008-2012. MATERIAL AND METHODS: The study concerned a potential epidemic outbreak with suspected bTB transmission. 20 cows came from 3 herds in the same county located in the same province in southern Poland. RESULTS: 134 MTBC strains were identified. In MIRU-VNTR, all isolates showed the same genetic pattern 322532243421232. Based on molecular investigation, the characteristics of M. bovis strains isolated from cattle from 3 different herds confirmed the common source of this zoonotic disease. CONCLUSIONS: Although not bacteriologically proven, everything points to the fact that humans were the vector of bovine tuberculosis transmission between herds. This finding confirms transmission between 3 cattle herds in the Malopolskie Province in southern Poland (Podhale). The outbreak of tuberculosis in animals finally compromised public health.


Assuntos
Vetores de Doenças , Mycobacterium bovis/isolamento & purificação , Tuberculose Bovina/microbiologia , Tuberculose/microbiologia , Zoonoses/transmissão , Animais , Bovinos , Humanos , Mycobacterium bovis/classificação , Mycobacterium bovis/genética , Polônia , Tuberculose/transmissão , Tuberculose Bovina/transmissão , Zoonoses/microbiologia
5.
Medicine (Baltimore) ; 98(33): e16771, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415377

RESUMO

The cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) is a bioactive component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS activates the innate immune system through various pattern recognition receptors and is expected to elicit antigen-specific cellular immune responses when co-administered with tumor antigens. To determine the recommended dose (RD) of BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.The primary endpoint was the proportion of treatment-related adverse events (AEs) at each BCG-CWS dose. The secondary endpoints were immune responses and clinical effects. A BCG-CWS dose of 50, 100, or 200 µg/body was administered intradermally on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For the escalation of a dose level, 3 + 3 design was used.Study subjects were 18 patients with advanced WT1-expressing cancers refractory to standard anti-cancer therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients at a dose of 200 µg although no serious treatment-related systemic AEs were observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. Some patients demonstrated the induction of the CD4 T cell subset and its differentiation from the naïve to memory phenotype, resulting in a tumor response.The RD of BCG-CWS was determined to be 100 µg/body. This dose was well tolerated and showed promising clinical effects with the induction of an appropriate immune response.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Esqueleto da Parede Celular/uso terapêutico , Mycobacterium bovis , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Vacina BCG/administração & dosagem , Contagem de Linfócito CD4 , Esqueleto da Parede Celular/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
6.
BMC Vet Res ; 15(1): 262, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349832

RESUMO

BACKGROUND: Dairy cattle movement could be a major risk factor for the spread of bovine tuberculosis (BTB) in emerging dairy belts of Ethiopia. Dairy cattle may be moved between farms over long distances, and hence understanding the route and frequency of the movements is essential to establish the pattern of spread of BTB between farms, which could ultimately help to inform policy makers to design cost effective control strategies. The objective of this study was, therefore, to investigate the network structure of dairy cattle movement and its influence on the transmission and prevalence of BTB in three emerging areas among the Ethiopian dairy belts, namely the cities of Hawassa, Gondar and Mekelle. METHODS: A questionnaire survey was conducted in 278 farms to collect data on the pattern of dairy cattle movement for the last 5 years (September 2013 to August 2018). Visualization of the network structure and analysis of the relationship between the network patterns and the prevalence of BTB in these regions were made using social network analysis. RESULTS: The cattle movement network structure display both scale free and small world properties implying local clustering with fewer farms being highly connected, at higher risk of infection, with the potential to act as super spreaders of BTB if infected. Farms having a history of cattle movements onto the herds were more likely to be affected by BTB (OR: 2.2) compared to farms not having a link history. Euclidean distance between farms and the batch size of animals moved on were positively correlated with prevalence of BTB. On the other hand, farms having one or more outgoing cattle showed a decrease on the likelihood of BTB infection (OR = 0.57) compared to farms which maintained their cattle. CONCLUSION: This study showed that the patterns of cattle movement and size of animal moved between farms contributed to the potential for BTB transmission. The few farms with the bulk of transmission potential could be efficiently targeted by control measures aimed at reducing the spread of BTB. The network structure described can also provide the starting point to build and estimate dynamic transmission models for BTB, and other infectious diseases.


Assuntos
Criação de Animais Domésticos/métodos , Indústria de Laticínios/estatística & dados numéricos , Tuberculose Bovina/epidemiologia , Animais , Bovinos , Análise por Conglomerados , Etiópia/epidemiologia , Mycobacterium bovis , Prevalência , Fatores de Risco , Inquéritos e Questionários , Transportes , Tuberculose Bovina/prevenção & controle
7.
Prev Vet Med ; 169: 104700, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311648

RESUMO

The QuantiFERON®-TB Gold (QFT) stimulation platform for cytokine release is a novel approach for diagnosis of bovine tuberculosis in wildlife species. Plasma interferon gamma (IFN-γ) is routinely measured to detect immune sensitization to Mycobacterium bovis. However, the cytokine interferon gamma-inducible protein 10 (IP-10) has been proposed as an alternative, more sensitive, diagnostic biomarker. In this study, we investigated the use of the QFT system with measurement of IFN-γ and IP-10 in parallel to identify M. bovis-infected African buffaloes. The test results of either biomarker in a cohort of M. bovis-unexposed buffaloes (n = 70) led to calculation of 100% test specificity. Furthermore, in cohorts of M. bovis culture-positive (n = 51) and M. bovis-suspect (n = 22) buffaloes, the IP-10 test results were positive in a greater number of animals than the number based on the IFN-γ test results. Most notably, when the biomarkers were measured in parallel, the tests identified all M. bovis culture-positive buffaloes, a result neither the single comparative intradermal tuberculin test (SCITT) nor Bovigam® IFN-γ release assay (IGRA) achieved, individually or in parallel. These findings demonstrate the diagnostic potential of this blood-based assay to identify M. bovis-infected African buffaloes and a strategy to maximise the detection of infected animals while maintaining diagnostic specificity and simplifying test procedures.


Assuntos
Biomarcadores/sangue , Búfalos/sangue , Quimiocina CXCL10/isolamento & purificação , Interferon gama/isolamento & purificação , Mycobacterium bovis/isolamento & purificação , Tuberculose/veterinária , Animais , Animais Selvagens , Antígenos de Bactérias/sangue , Estudos de Coortes , Sensibilidade e Especificidade , África do Sul , Tuberculose/sangue , Tuberculose/diagnóstico
8.
J Dairy Sci ; 102(9): 8405-8409, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301842

RESUMO

Different mycobacterial species are encountered in bovine medicine. The fastidiously growing mycobacteria (Mycobacterium bovis as the cause of bovine tuberculosis, and Mycobacterium avium ssp. paratuberculosis, MAP, as the cause of paratuberculosis) are well known and targeted in eradication/control or monitoring programs in different countries, whereas the rapidly growing species is only rarely identified from bovine disease. The latter have occasionally been reported as the cause of bovine clinical mastitis, but recent reports are scarce. In this study, Mycolicibacterium smegmatis (basonym Mycobacterium smegmatis) was identified as cause of granulomatous, relapsing clinical mastitis in 2 cows from one Belgian dairy herd. Milk, blood, and fecal samples were collected, as well as tissue samples after the cows were culled. Serological analysis conducted on milk and serum samples resulted in positive reactions for MAP, but negative for Mycobacterium bovis. Production of IFN-γ showed sensitization with mycobacteria or similar organisms, other than M. bovis, in one cow. Detection of MAP by bacteriological culture and IS900-based quantitative PCR on milk and feces remained negative. In conclusion, this paper describes M. smegmatis as a cause of bovine clinical mastitis in Belgium and suggests cross-reactivity of the intramammary M. smegmatis infection with routinely used serological tests for MAP.


Assuntos
Doenças dos Bovinos/microbiologia , Mastite Bovina/microbiologia , Mycobacterium smegmatis , Paratuberculose/diagnóstico , Animais , Bélgica , Bovinos , Doenças dos Bovinos/diagnóstico , Reações Cruzadas , Fezes/microbiologia , Feminino , Leite/microbiologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Mycobacterium bovis/imunologia , Mycobacterium smegmatis/imunologia , Paratuberculose/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Tuberculose Bovina
9.
BMC Infect Dis ; 19(1): 568, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262260

RESUMO

BACKGROUND: With the aim of preparing a more effective, safe and economical vaccine for tuberculosis, inhalable live mycobacterium formulations were evaluated. METHODS: Alginate particles in the size range of 2-4 µm were prepared by encapsulating live Bacille Calmette-Guérin (BCG) and "Mycobacterium indicus pranii" (MIP). These particles were characterized for their size, stability and release profile. Mice were immunized with liquid aerosol or dry powder aerosol (DPA) alginate encapsulated mycobacterium particles and their in-vitro recall response and infection with mycobacterium H37Rv were investigated. RESULTS: It was found that the DPA of alginate encapsulated mycobacterium particles invoked superior immune response and provided higher protection in mice than the liquid aerosol. The BCG encapsulated in alginate particles (BEAP) and MIP encapsulated in alginate particles (MEAP) were engulfed by bone marrow dendritic cells (BMDCs) and co-localized with lysosome. The MEAP/BEAP activated BMDCs exhibited higher chemotaxis movement and had enhanced ability of antigen presentation to T cells. The in-vitro recall response of BEAP/MEAP immunized mice when compared in terms of proliferation index and Interferon gamma (IFN-gamma) released by splenocytes and mediastinal lymph node cells was found to be higher than mice immunized by liquid aerosol of BCG/MIP. Finally, different groups of immunized mice were infected with M. tb H37Rv and after 16 weeks the Colony forming units (CFUs) in lung and spleen estimated. The bacilli burden in the BEAP/MEAP immunized mice was significantly less than the respective liquid aerosol immunized mice and the histopathology of BEAP/MEAP immunized mice lungs showed very little damage. CONCLUSIONS: These inhale-able vaccines formulation of alginate coated live mycobacterium are more immunogenic as compared to the aerosol of bacilli and they provide better protection in mice when infected with H37Rv.


Assuntos
Aerossóis/administração & dosagem , Pulmão/imunologia , Vacinas contra a Tuberculose/farmacologia , Tuberculose/prevenção & controle , Alginatos/química , Animais , Vacina BCG/imunologia , Sistemas de Liberação de Medicamentos/métodos , Interferon gama/imunologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Complexo Mycobacterium avium/química , Complexo Mycobacterium avium/imunologia , Mycobacterium bovis/química , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Baço/microbiologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Tuberculose/imunologia , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/imunologia , Vacinação/métodos
10.
PLoS Pathog ; 15(6): e1007866, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31188899

RESUMO

The gastric lamina propria of mice that have been experimentally infected with the pathobiont Helicobacter pylori hosts a dense network of myeloid cells that includes BATF3-dependent CD103+ dendritic cells (DCs). We show here that CD103+ DCs are strictly required for gastric Th1 responses to H. pylori and for H. pylori infection control. A similar dependence of type 1 immunity on CD103+ DCs is observed in a Mycobacterium bovis BCG infection model, and in a syngeneic colon cancer model. Strikingly, we find that not only the expansion and/or recruitment of Th1 cells, but also of peripherally induced, neuropilin-negative regulatory T-cells to sites of infection requires BATF3-dependent DCs. A shared feature of the examined models is the strongly reduced production of the chemokines and CXCR3 ligands CXCL9, 10 and 11 in BATF3-deficient mice. The results implicate BATF3-dependent DCs in the recruitment of CXCR3+ effector and regulatory T-cells to target tissues and in their local expansion.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/imunologia , Células Dendríticas/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Mycobacterium bovis/imunologia , Proteínas Repressoras/imunologia , Linfócitos T Reguladores/imunologia , Tuberculose/imunologia , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linhagem Celular Tumoral , Quimiocinas CXC/genética , Quimiocinas CXC/imunologia , Células Dendríticas/microbiologia , Células Dendríticas/patologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Camundongos , Camundongos Knockout , Receptores CXCR3/genética , Receptores CXCR3/imunologia , Proteínas Repressoras/genética , Linfócitos T Reguladores/microbiologia , Linfócitos T Reguladores/patologia , Tuberculose/genética , Tuberculose/patologia
12.
Scand J Immunol ; 90(4): e12798, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31179555

RESUMO

CD40 ligand (CD40L) deficiency is a rare but life-threatening primary immunodeficiency caused by mutations in the CD40L gene. Here, we investigated a cohort of 40 genetically diagnosed CD40L-deficient patients from the Chinese mainland, analysed their clinical and genetic data, and examined CD40L expression, the proportion of T cell subsets, B cell subsets and T follicular helper (Tfh) cells. The aim was to provide a complete picture of CD40L deficiency. Initial presentations of the patient cohort mainly involved recurrent fever (47.5%) and sinopulmonary infection (42.5%). Life-threatening infections (42.5%), caused by various pathogens, were the most serious threats faced by CD40L-deficient patients, while neutropenia (57.5%) remained the most common complication. Opportunistic infections, including Pneumocystis carinii pneumonia and invasive fungal disease associated with Talaromyces marneffei, were also common in the cohort. In addition, seven patients (17.5%) suffered BCGitis/BCGosis, which is a major problem facing a planned immunization programme in China. It was intriguing that reduced IgM levels were observed in 12.5% of patients, while normal or elevated IgA levels were shown in 47.5% of patients. Thirty-seven unique mutations were identified in 40 patients; of these, 10 were novel. Furthermore, we observed a lower percentage of NK cells, Tfh cells, and central memory CD4+ T cells, and an extremely small class-switched memory B cell population, in CD40L-deficient patients. Patients who underwent hematopoietic stem cell transplantation experienced better disease remission. Taken together, our data establish the largest database about CD40L deficiency in China and provide genetic, immunologic and clinical information about Chinese CD40L-deficient patients.


Assuntos
Ligante de CD40/genética , Síndromes de Imunodeficiência/imunologia , Células Matadoras Naturais/imunologia , Pneumopatias Fúngicas/imunologia , Pneumocystis carinii/fisiologia , Pneumonia por Pneumocystis/imunologia , Linfócitos T/imunologia , Talaromyces/fisiologia , China , Estudos de Coortes , Febre , Humanos , Imunoglobulina M/sangue , Síndromes de Imunodeficiência/genética , Memória Imunológica , Pneumopatias Fúngicas/genética , Masculino , Mycobacterium bovis , Pneumonia por Pneumocystis/genética , Adulto Jovem
13.
BMC Vet Res ; 15(1): 188, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174546

RESUMO

BACKGROUND: Both bovine tuberculosis (TB) and paratuberculosis (PTB) are serious and widespread bacterial infections affecting many domestic and wild animal species. However, current vaccines do not confer complete protection and cause interference with other diagnostics tests, including bovine TB. Therefore, the development of "Differentiating Infected from Vaccinated Animals" (DIVA) tests are a pressing need. In this study, we have tested the feasibility of mycobacterial extracellular vesicles (EVs) as potential source of biomarkers to discriminate between Mycobacterium bovis infected, Mycobacterium avium subsp. paratuberculosis (MAP) infected and MAP-vaccinated cows. We have, initially, characterized vesicle production in the two most medically relevant species of mycobacteria for livestock, MAP and M. bovis, for being responsible for tuberculosis (TB) and paratuberculosis (PTB). RESULTS: Our results indicate that these two species produce EVs with different kinetics, morphology and size distribution. Analysis of the immunogenicity of both type of EVs showed some cross reactivity with sera from PTB+ and TB+ cows, suggesting a limited diagnostic capacity for both EVs. Conversely, we noticed that Mycobacterium tuberculosis (Mtb) EVs showed some differential reactivity between sera from MAP-vaccinated or PTB+ cows from TB+ ones. Mass spectrometry analysis (MS) identified a 19-kDa EV-associated lipoprotein as the main source of the differential reactivity. CONCLUSIONS: LpqH could be a good plasma biomarker with capacity to distinguish PTB+ or MAP-vaccinated cows from cows infected with TB.


Assuntos
Doenças dos Bovinos/microbiologia , Vesículas Extracelulares/química , Lipoproteínas/análise , Mycobacterium tuberculosis/química , Paratuberculose/diagnóstico , Tuberculose Bovina/diagnóstico , Animais , Vacinas Bacterianas , Biomarcadores/sangue , Bovinos , Reações Cruzadas , Mycobacterium avium subsp. paratuberculosis/química , Mycobacterium bovis/química , Vacinação/veterinária
14.
Vet Res Commun ; 43(3): 155-164, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222520

RESUMO

Cattle are the domestic animal reservoir for Mycobacterium bovis (M. bovis) which also affects other domestic animals, several wildlife species and humans leading to tuberculosis. The study area is in a resource-poor community that is surrounded by several game parks, where M. bovis infection has been previously diagnosed in wildlife. A cross-sectional study was carried out to determine the prevalence of M. bovis infection in 659 cattle from a total of 192 traditionally managed herds using the BOVIGAM® interferon gamma assay (IFN-γ). Infection was confirmed by post mortem examination and M. bovis isolation from three test-positive cattle. Genotyping of the M. bovis isolates was done using spoligotyping and VNTR (variable number of tandem repeats typing). The apparent M. bovis prevalence rate in cattle at animal level was 12% with a true population prevalence of 6% (95% Confidence interval (C.I) 3.8 to 8.1) and a herd prevalence of 28%. Spoligotyping analysis revealed that the M. bovis isolates belonged to spoligotype SB0130 and were shared with wildlife. Three VNTR profiles were identified among the SB0130 isolates from cattle, two of which had previously been detected in buffalo in a game reserve adjacent to the study area. The apparent widespread presence of M. bovis in the cattle population raises a serious public health concern and justifies further investigation into the risk factors for M. bovis transmission to cattle and humans. Moreover, there is an urgent need for effective bTB control measures to reduce infection in the communal cattle and prevent its spread to uninfected herds.


Assuntos
Tuberculose Bovina/epidemiologia , Animais , Animais Selvagens/microbiologia , Bovinos , Genótipo , Gado/microbiologia , Repetições Minissatélites/genética , Mycobacterium bovis/genética , Prevalência , Fatores de Risco , África do Sul/epidemiologia
16.
BMC Infect Dis ; 19(1): 532, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208362

RESUMO

BACKGROUND: There is controversy regarding the relative influence of 'exogenous' versus 'endogenous' factors on the risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease in children. METHODS: We conducted a cross-sectional analysis to identify risk factors for active tuberculosis in QuantiFERON®-TB Gold (QFT-G)-positive children aged 6-13 years attending 18 schools in Ulaanbaatar, Mongolia. Children underwent clinical and radiological screening for active tuberculosis, and data relating to potential risk factors for disease progression were collected by questionnaire and determination of serum 25-hydroxyvitamin D (25[OH]D) concentrations. Risk ratios were calculated using generalized estimating equations with adjustment for potential confounders. RESULTS: 129/938 (13.8%) QFT-positive children were diagnosed with active tuberculosis. Risk of active tuberculosis was independently associated with household exposure to pulmonary TB (adjusted risk ratio [aRR] 2.40, 95% CI 1.74 to 3.30, P < 0.001), month of sampling (adjusted risk ratio [aRR] for March-May vs. June-November 3.31, 95% CI 1.63 to 6.74, P < 0.001; aRR for December-February vs. June-November 2.53, 95% CI 1.23 to 5.19, P = 0.01) and active smoking by the child (aRR 5.23, 95% CI 2.70 to 10.12, P < 0.001). No statistically significant independent association was seen for age, sex, socio-economic factors, presence of a Bacillus Calmette-Guérin (BCG) scar, tobacco exposure or vitamin D status. CONCLUSIONS: Household exposure to active TB, winter or spring season and active smoking were independently associated with risk of active tuberculosis in QFT-positive children. Our findings highlight the potentially high yield of screening child household contacts of infectious index cases for active tuberculosis in low- and middle-income countries.


Assuntos
Tuberculose Latente/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Criança , Estudos Transversais , Progressão da Doença , Feminino , Testes Hematológicos/métodos , Humanos , Tuberculose Latente/diagnóstico , Masculino , Programas de Rastreamento , Mongólia/epidemiologia , Mycobacterium bovis , Razão de Chances , Fatores de Risco , Fumar , Inquéritos e Questionários , Tuberculose Pulmonar/diagnóstico , Vitamina D/análogos & derivados , Vitamina D/sangue
17.
Artigo em Inglês | MEDLINE | ID: mdl-31174696

RESUMO

The analysis of haptoglobin (Hp) serum concentration is a very sensitive, but non-specific, indicator of inflammation or infection. Methods to accurately diagnose infection in vivo in wildlife are usually constrained by low sensitivity due to the effects of stress on individual immune response and the challenging logistics of performing tests in the wild. Firstly, we sought to determine serum Hp concentration in red deer (Cervus elaphus) naturally infected with bovine tuberculosis (TB). Secondly, we assessed the complementary diagnostic value of serum Hp levels in conjunction with the cervical comparative skin test (CCT) performed in a subsample (n = 33). Serum Hp concentrations were significantly higher in TB-infected individuals (based on the presence of macroscopic lesions confirmed by culture) compared to those uninfected. In addition, serum Hp significantly changed with the type of animal handling, with captured and handled animals showing higher levels of Hp than hunted animals. Four out of 6 TB positive individuals that tested negative to the CCT (false negatives) showed Hp levels higher than the 95th percentile of healthy animals. These findings indicate that an acute phase response develops in animals with TB. In this paper, we demonstrate for the first time that an acute phase protein can provide a complementary assessment for specific diagnosis tests in wild species.


Assuntos
Cervos/imunologia , Haptoglobinas/imunologia , Tuberculose Bovina/sangue , Tuberculose Bovina/diagnóstico , Animais , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Bovinos , Cervos/microbiologia , Ensaio de Imunoadsorção Enzimática , Mycobacterium bovis , Testes Cutâneos/métodos
18.
Trop Anim Health Prod ; 51(7): 1801-1805, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197725

RESUMO

The occurrence of Mycobacterium bovis infection in wildlife places at risk livestock, public health, and ecosystems that house endangered species. However, data on wild species that may act as possible reservoirs in the Americas are scarce. This systematic review analyses the available data on wildlife in the Americas regarding the infection by M. bovis. We searched articles published in indexed journals using the keywords: "Mycobacterium bovis," "wild," and "animals". After applying the keywords using online databases, during March and August of 2018, we found 12 articles which encompassed 15 species of wild animals, of which three consisted of wild ruminants. The evidence showed that M. bovis is present among the wild animals in the Americas. The methodological limitations for diagnosing M. bovis in wild animals are many, demanding the development of new and more precise tools. Furthermore, new researches are needed to elucidate the role of the wild animals in the epidemiology of M. bovis and its possible impact on production animals and public health.


Assuntos
Animais Selvagens , Artiodáctilos , Carnívoros , Didelphis , Mycobacterium bovis/fisiologia , Tuberculose Bovina/epidemiologia , Américas , Animais , Bovinos , América do Sul/epidemiologia , Tuberculose Bovina/microbiologia , Estados Unidos/epidemiologia
19.
Eur J Histochem ; 63(2)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243942

RESUMO

The limited availability of rapid and reliable flow cytometry-based assays for ex vivo quantification of autophagy has hampered their clinical applications for studies of diseases pathogenesis or for the implementation of autophagy-targeting therapies. To this aim, we modified and improved the protocol of a commercial kit developed for quantifying the microtubule-associated protein 1A/1B light chain 3B (LC3), the most reliable marker for autophagosomes currently available. The protocol modifications were set up measuring the autophagic flux in neoplastic (THP-1 cells) and primary cells (peripheral blood mononuclear cells; PBMC) of healthy donors. Moreover, PBMC of active tuberculosis (TB) patients were stimulated with the Mycobacterium tuberculosis purified protein derivatives or infected with live Mycobacterium bovis bacillus Calmette-Guerin (BCG). We found that the baseline median fluorescent intensity (MFI) of THP-1 cells changed depending on the time of sample acquisition to the flow cytometer. To solve this problem, a fixation step was introduced in different stages of the assay's protocol, obtaining more reproducible and sensitive results when a post-LC3 staining fixation was performed, in either THP1 or PBMC. Furthermore, since we found that results are influenced by the type and the dose of the lysosome inhibitor used, the best dose of Chloroquine for LC3 accumulation were set up in either THP-1 cells or PBMC. Finally, applying these experimental settings, we measured the autophagic flux in CD14+ cells from active TB patients' PBMC upon BCG infection. In conclusion, our data indicate that the protocol modifications here described in this work improve the stability and accuracy of a flow cytometry-based assay for the evaluation of autophagy, thus assuring more standardised cell analyses.


Assuntos
Autofagia , Citometria de Fluxo/métodos , Proteínas Associadas aos Microtúbulos/análise , Autofagia/efeitos dos fármacos , Proteínas de Bactérias/farmacologia , Cloroquina/farmacologia , Fluorescência , Humanos , Leucócitos Mononucleares/microbiologia , Mycobacterium bovis/química , Coloração e Rotulagem , Células THP-1
20.
Nat Commun ; 10(1): 2647, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201321

RESUMO

Growth and division by most bacteria requires remodelling and cleavage of their cell wall. A byproduct of this process is the generation of free peptidoglycan (PG) fragments known as muropeptides, which are recycled in many model organisms. Bacteria and hosts can harness the unique nature of muropeptides as a signal for cell wall damage and infection, respectively. Despite this critical role for muropeptides, it has long been thought that pathogenic mycobacteria such as Mycobacterium tuberculosis do not recycle their PG. Herein we show that M. tuberculosis and Mycobacterium bovis BCG are able to recycle components of their PG. We demonstrate that the core mycobacterial gene lpqI, encodes an authentic NagZ ß-N-acetylglucosaminidase and that it is essential for PG-derived amino sugar recycling via an unusual pathway. Together these data provide a critical first step in understanding how mycobacteria recycle their peptidoglycan.


Assuntos
Acetilglucosaminidase/metabolismo , Proteínas de Bactérias/metabolismo , Mycobacterium bovis/metabolismo , Mycobacterium tuberculosis/metabolismo , Peptidoglicano/metabolismo , Antibióticos Antituberculose/farmacologia , Parede Celular/química , Parede Celular/metabolismo , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Ácidos Murâmicos/metabolismo , Muramidase/farmacologia , Mycobacterium bovis/química , Mycobacterium tuberculosis/química , Peptidoglicano/química
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