RESUMEN
A 23-y-old gelding was presented to a veterinary teaching hospital with a history of chronic, refractory diarrhea. Clinically, the horse was in poor body condition, with a thickened and corrugated large intestine identified by transcutaneous abdominal ultrasonography. At postmortem examination following euthanasia, the large colon and cecum had segmental thickening of the intestinal wall with innumerable mucosal ulcers and prominent polypoid mucosal masses. Many mesenteric and hepatic lymph nodes were enlarged. Histology revealed granulomatous and ulcerative typhlocolitis and granulomatous lymphadenitis with myriad acid-fast, variably gram-positive, intrahistiocytic bacilli that stained by immunohistochemistry for mycobacteria. Molecular testing by PCR and sequencing identified the causative agent as Mycobacterium genavense, which is an unusual presentation of infection in a horse.
Asunto(s)
Enfermedades de los Caballos , Mycobacterium , Animales , Caballos , Enfermedades de los Caballos/microbiología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/diagnóstico , Mycobacterium/aislamiento & purificación , Mycobacterium/genética , Masculino , Infecciones por Mycobacterium/veterinaria , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Infecciones por Mycobacterium/diagnóstico , Tiflitis/veterinaria , Tiflitis/patología , Tiflitis/microbiología , Tiflitis/diagnóstico , Colitis/veterinaria , Colitis/microbiología , Colitis/patología , Resultado FatalAsunto(s)
Complicaciones de la Diabetes , Dermatosis Facial/microbiología , Infecciones por Mycobacterium/diagnóstico , Mycobacterium , Enfermedades Cutáneas Bacterianas/diagnóstico , Úlcera Cutánea/microbiología , Anciano , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/inmunología , Diabetes Mellitus/sangre , Diabetes Mellitus/inmunología , Dermatosis Facial/diagnóstico , Dermatosis Facial/patología , Femenino , Control Glucémico , Humanos , Huésped Inmunocomprometido , Infecciones por Mycobacterium/patología , Enfermedades Cutáneas Bacterianas/patología , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/patologíaRESUMEN
Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.
Asunto(s)
Enfermedad Granulomatosa Crónica/inmunología , Enfermedad Granulomatosa Crónica/microbiología , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Infecciones por Mycobacterium/inmunología , Animales , Enfermedad Granulomatosa Crónica/patología , Humanos , Macrófagos/patología , Infecciones por Mycobacterium/patologíaRESUMEN
We previously reported that M. tb on its own as well as together with HIV inhibits macrophage apoptosis by upregulating the expression of Bcl2 and Inhibitor of Apoptosis (IAP). In addition, recent reports from our lab showed that stimulation of either macrophages or BMDCs results in the significant upregulation of Bcl2. In this report, we delineate the role of Bcl2 in mediating defense responses from dendritic cells (BMDCs) during mycobacterial infection. Inhibiting Bcl2 led to a significant decrease in intracellular bacterial burden in BMDCs. To further characterize the role of Bcl2 in modulating defense responses, we inhibited Bcl2 in BMDCs as well as human PBMCs to monitor their activation and functional status in response to mycobacterial infection and stimulation with M. tb antigen Rv3416. Inhibiting Bcl2 generated protective responses including increased expression of co-stimulatory molecules, oxidative burst, pro-inflammatory cytokine expression and autophagy. Finally, co-culturing human PBMCs and BMDCs with antigen-primed T cells increased their proliferation, activation and effector function. These results point towards a critical role for Bcl2 in regulating BMDCs defense responses to mycobacterial infection.
Asunto(s)
Células Dendríticas/inmunología , Inmunidad , Macrófagos/inmunología , Infecciones por Mycobacterium/inmunología , Mycobacterium bovis/inmunología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Apoptosis , Autofagia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Células Dendríticas/microbiología , Células Dendríticas/patología , Femenino , Humanos , Macrófagos/metabolismo , Macrófagos/microbiología , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Infecciones por Mycobacterium/metabolismo , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Proteínas Proto-Oncogénicas c-bcl-2/genéticaRESUMEN
Flow cytometry enables the measurement of tens of features on individual cells from complex mixtures. Flow cytometry enables high-throughput quantification of cell size, gene and protein expression. In the case of studies of host-pathogen interactions, this tool provides a facile way of identifying cells that have been successfully infected by a pathogen. Several recent technological advances have greatly improved throughput and the number of features that can be simultaneously monitored by this technique. Here, we describe common workflows to study Mycobacterium tuberculosis heterogeneity and host-M. tuberculosis interactions using flow cytometry and related technologies.
Asunto(s)
Citometría de Flujo/métodos , Interacciones Huésped-Patógeno , Macrófagos/inmunología , Macrófagos/microbiología , Infecciones por Mycobacterium/microbiología , Mycobacterium tuberculosis/patogenicidad , Humanos , Infecciones por Mycobacterium/inmunología , Infecciones por Mycobacterium/patologíaRESUMEN
Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.
Asunto(s)
Autofagia/efectos de los fármacos , Infecciones por Mycobacterium/tratamiento farmacológico , Infecciones por Mycobacterium/patología , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/patología , Descubrimiento de Drogas , Humanos , MycobacteriumRESUMEN
Short-lived killifishes of the genus Nothobranchius Peters, 1868 (Cyprinodontiformes) are considered promising model organisms for biomedical research on ageing and tumorigenesis. We conducted histopathological analysis of 411 adult individuals from three Nothobranchius species to study details on spontaneous age-related neoplastic lesions. Light microscopy based on H&E and toluidine blue-stained sections revealed (a) non-proliferative liver changes with pronounced vacuolation of hepatocytes; (b) proliferation of kidney haemopoietic tissue contributing to excretory system damage; (c) proliferation of splenic mononuclear haemoblasts accompanied by reduced erythropoiesis; (d) proliferation of mononuclear cell aggregates in the liver parenchyma; and (e) rare occurrence of hepatocellular adenomas. Ziehl-Neelsen (ZN) staining revealed that the proliferative lesions are a host defence response to mycobacterial infections manifested by activation of the mononuclear phagocytic system and atypical granulomatous inflammatory reaction. 16S rRNA analysis identified three species of Mycobacterium in our samples. Our findings turn attention to lesions which mimic neoplasms by their gross appearance and question the light microscopic interpretation of lesions unless differential ZN staining is included. Beyond the limitations of our morphological approach, the intensity of mycobacterial infections is a challenging opportunity for research into the molecular-genetic background of the mononuclear phagocytic system reaction in Nothobranchius killifish.
Asunto(s)
Ciprinodontiformes , Enfermedades de los Peces/patología , Mycobacteriaceae/aislamiento & purificación , Infecciones por Mycobacterium/veterinaria , Mycobacterium marinum/aislamiento & purificación , Neoplasias/veterinaria , Animales , Femenino , Masculino , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Neoplasias/diagnóstico , Neoplasias/etiología , Neoplasias/patología , ARN Bacteriano/análisis , ARN Ribosómico 16S/análisisAsunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Infecciones por Mycobacterium/diagnóstico por imagen , Mycobacterium/aislamiento & purificación , Neoplasias Encefálicas/microbiología , Neoplasias Encefálicas/patología , Humanos , Inmunocompetencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patologíaRESUMEN
We detail a novel presentation of tuberculosis associated with intestinal perforation in an endangered Australian sea lion (Neophoca cinerea) from South Australian waters and confirm the presence of this disease in the region of highest pup production. In February 2017, a 3-yr-old juvenile male died shortly after hauling out at the Kingscote beach on Kangaroo Island. On postmortem examination, we found a mid-jejunal intestinal perforation and partial obstruction (from a strangulating fibrous and granulomatous mesenteric mass), a marked multicentric abdominal fibrosing granulomatous lymphadenitis, and a large volume serosanguinous peritoneal effusion. Acid-fast bacteria were detected postmortem in cytologic preparations of the mesenteric lymph node and in histologic sections of jejunum and the encircling mass. Mycobacterial infection was confirmed by positive culture after 3 wk. Molecular typing using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing with 12-locus analysis identified Mycobacterium pinnipedii. This case highlights the need for vigilance of zoonotic disease risk when handling pinnipeds, including in the absence of specific respiratory signs or grossly apparent pulmonary pathology. Increased serologic population surveillance is recommended to assess the species' risk from this and other endemic diseases, especially given its endangered status.
Asunto(s)
Especies en Peligro de Extinción , Perforación Intestinal/veterinaria , Infecciones por Mycobacterium/veterinaria , Leones Marinos/microbiología , Animales , Animales Salvajes , Resultado Fatal , Granuloma/microbiología , Granuloma/patología , Granuloma/veterinaria , Obstrucción Intestinal/microbiología , Obstrucción Intestinal/veterinaria , Perforación Intestinal/microbiología , Perforación Intestinal/patología , Infecciones Intraabdominales/microbiología , Infecciones Intraabdominales/patología , Infecciones Intraabdominales/veterinaria , Masculino , Mycobacterium/clasificación , Mycobacterium/genética , Mycobacterium/aislamiento & purificación , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patologíaRESUMEN
Immunofluorescence is indispensable to monitor redistribution of proteins involved in phagosome-lysosome association pathway-relevant (P-LApr) proteins. The software digitizing the signals of these proteins in an unbiased and automated manner is generally costly and not widely available. The open-source ImageJ plugin EzColocalization, which is for co-localization analysis of reporters in cells, was not straightforward and sufficient for such analysis. We describe here the input of custom Java code in a novel tailored protocol using EzColocalization to digitize the signals of punctum-distributed P-LApr proteins co-localized with phagosomes and to calculate percentages of phagosomes engaged. We showed that SYBR Gold nucleic acid dye could visualize intracellular mycobacteria that did not express a fluorescent protein. This protocol was validated by showing that IFN-γ enhanced the co-localization of a punctum-distributed P-LApr protein (LC3) with Mycobacterium bovis BCG in the monocyte/macrophage-like RAW264.7 cells and that there was greater co-localization of LC3 with BCG than with M. tuberculosis H37Rv in bone marrow-derived macrophages (BMDMs). Although BCG and a derived strain (rBCG-PA) showed a similarly high degree co-localization with LC3 in BMDMs, in RAW264.7 cells BCG showed much less co-localization with LC3 than rBCG-PA indicating the need for caution in interpreting biological significance from studies in cell lines.
Asunto(s)
Lisosomas/microbiología , Infecciones por Mycobacterium/patología , Mycobacterium/aislamiento & purificación , Fagosomas/microbiología , Animales , Técnica del Anticuerpo Fluorescente , Procesamiento de Imagen Asistido por Computador , Lisosomas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Infecciones por Mycobacterium/microbiología , Fagosomas/patología , Células RAW 264.7RESUMEN
OBJECTIVES: Diagnosis of mycobacterial infections poses significant challenges in anatomic pathology. We recently described the use of antimycobacteria immunohistochemistry (IHC) as a sensitive, efficient diagnostic tool and now report the clinical performance of this assay among general, noninfectious disease pathology-trained anatomic pathologists. METHODS: Over a 2-year period, all cases were retrospectively identified in which mycobacterial IHC was performed during routine diagnostic workup. RESULTS: From October 2017 to September 2019, mycobacterial IHC was evaluated for 267 cases, resulting in 58 (22%) positive stains. Compared with culture and molecular results, the sensitivity and specificity of IHC were 52% and 80%, respectively. IHC performed significantly better than acid-fast bacilli (AFB) staining (Ziehl-Neelsen) (P < .0001; sensitivity 21%, specificity 92%) but similarly to modified AFB staining (mAFB; Fite-Faraco) (P = .9; sensitivity 61%, specificity 84%). In cases with discordant IHC and mAFB staining, there were no differences in rates of culture or polymerase chain reaction-confirmed positivity. CONCLUSIONS: Mycobacterial IHC was well adopted with superior clinical performance to AFB and comparable performance to mAFB. These results support the use of IHC as an adjunctive tool in the diagnosis of mycobacterial infections and suggests its potential role as a rapid screening test for molecular testing.
Asunto(s)
Inmunohistoquímica , Infecciones por Mycobacterium/diagnóstico , Mycobacterium tuberculosis/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Pulmón/microbiología , Pulmón/patología , Tejido Linfoide/microbiología , Tejido Linfoide/patología , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Piel/microbiología , Piel/patología , Adulto JovenRESUMEN
Bovine Nodular Thelitis (BNT) is a granulomatous dermatitis of teat skin associated with acid-fast bacilli. A similar condition has been recorded in a dairy goat flock in France recently. The causative agent was shown to be related to the leprosy-causing bacilli Mycobacterium leprae and M. lepromatosis, then sequenced and named M. uberis. Following the initial report in goats, the aim of this study was to investigate new cases of Caprine Nodular Thelitis (CNT) in the same area to confirm the presence of M. uberis by molecular techniques and to get a better description of the clinical signs and of the affected flocks. Twenty-six animals (25 females and 1 male) from 11 flocks were included in the study. Lesions were located on the udder/teat skin (24/25), on the body skin (6/25) or on the scrotum skin (1/1). Udder skin lesions were circular, nodular and/or ulcerate covered with a crust and associated with supramammary lymph node enlargement. Body skin lesions were located at different parts of the body, showed large necrotizing ulcers with undetermined edges and were associated with regional lymph node enlargement. Histopathological results indicated granulomatous dermatitis and lymphadenitis of varying intensity with no acid-fast bacilli seen after Fite-Faraco staining. M. uberis DNA was amplified from 26 samples out of 47 (udder: 11/22; lymph node: 11/20; body: 4/5). The female goats were mostly older than 4 year of age and originated from breeding units characterized by large flock size and high proportion of goat in continuous lactation.
Asunto(s)
Enfermedades de las Cabras/patología , Mastitis/veterinaria , Infecciones por Mycobacterium/veterinaria , Mycobacterium/aislamiento & purificación , Animales , Femenino , Enfermedades de los Genitales Masculinos/microbiología , Enfermedades de los Genitales Masculinos/patología , Enfermedades de los Genitales Masculinos/veterinaria , Enfermedades de las Cabras/microbiología , Cabras , Masculino , Mastitis/microbiología , Mastitis/patología , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Escroto/patologíaRESUMEN
Infections by opportunistic non-tuberculous mycobacteria (NTM) are rising in global incidence. One emerging, slowly growing NTM is Mycobacterium haemophilum, which can cause skin, lung, bone, and soft tissue infections in immunocompromised patients as well as lymphadenitis in immunocompetent individuals. Detection of this microorganism is difficult using conventional culture-based methods and few reports have documented involvement of this pathogen within the central nervous system (CNS).We describe the neuropathologic autopsy findings of a 39-year-old man with AIDS who died secondary to M. haemophilum CNS infection. He initially presented with repeated bouts of pyrexia, nausea and vomiting, and altered mental status that required numerous hospitalizations. CSF infectious workups were consistently negative. His most recent admission identified hyperintensities within the brainstem by MRI and despite antibiotic therapies for suspected CNS infection, he died. Autopsy revealed a swollen brain with marked widening of the brainstem. Microscopic examination of the brain and spinal cord showed focal lymphohistiocytic infiltrates, gliosis and neuronal loss that were associated with acid-fast bacilli (AFB). The brainstem was the most severely damaged and AFB were found to congregate along arterial territories lending support to the notion of hematogenous spread as a mechanism for the organisms' dissemination. 16S rRNA sequencing on formalin-fixed paraffin-embedded tissue enabled post-mortem identification of M. haemophilum. This sequencing methodology may permit diagnosis on CSF intra-vitam.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Encefalitis Infecciosa/patología , Meningoencefalitis/patología , Infecciones por Mycobacterium/patología , Mycobacterium haemophilum , Adulto , Tronco Encefálico/patología , Humanos , MasculinoAsunto(s)
Enfermedad de Crohn/complicaciones , Infecciones por Mycobacterium/diagnóstico , Mycobacterium haemophilum/aislamiento & purificación , Enfermedades Cutáneas Bacterianas/diagnóstico , Anciano , Femenino , Humanos , Huésped Inmunocomprometido , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/patologíaRESUMEN
Mycobacterium africanum (MAF) is known to endemically cause up to 40-50% of all pulmonary TB in West Africa. The aim of this study was to compare MAF with Mycobacterium tuberculosis (MTB) with regard to time from symptom onset to TB diagnosis, and clinical and radiological characteristics. A cross-sectional study was conducted in Bamako, Mali, between August 2014 and July 2016. Seventy-seven newly diagnosed pulmonary TB patients who were naive to treatment were enrolled at Mali's University Clinical Research Center. Sputum cultures were performed to confirm the diagnosis and spoligotyping to identify the mycobacterial strain. Univariate and multivariate analyses were used to identify factors associated with disease progression. Overall, the frequency of female patients was 25% in MAF infection and only 10.0% in MTB infection (OR = 2.9), and MAF was more represented in patients aged ≥ 30 years (57.1% versus 36.7% [OR = 2.3]). More MAF- than MTB-infected patients had a history of a prior TB contact (32.1% versus 14.3% [OR = 2.8]). The mean duration between cough onset and TB diagnosis was 111 days (â¼3.7 months) for MAF and 72 days (â¼2.4 months) for MTB (P = 0.007). In a multivariate regression, weight loss (body mass index [BMI] < 18.5 kg/m2) and cough duration (> 4 months) were strongly associated with MAF infection (OR = 5.20 [1.49-18.26], P = 0.010, and 4.74 [1.2-18.58], P = 0.02), respectively. Our data show that MAF infection was significantly associated with lower BMI and a longer time between symptom onset and TB diagnosis than MTB. This supports the concept that MAF infection may have slower disease progression and less severe cough symptoms than MTB.
Asunto(s)
Infecciones por Mycobacterium/microbiología , Mycobacterium tuberculosis , Mycobacterium/clasificación , Tuberculosis/microbiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Malí/epidemiología , Persona de Mediana Edad , Infecciones por Mycobacterium/epidemiología , Infecciones por Mycobacterium/patología , Tuberculosis/epidemiología , Tuberculosis/patología , Adulto JovenAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Infecciones por Mycobacterium/complicaciones , Mycobacterium/aislamiento & purificación , Paniculitis Peritoneal/etiología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Adulto , Resultado Fatal , Infecciones por VIH/microbiología , Humanos , Huésped Inmunocomprometido , Masculino , Infecciones por Mycobacterium/patología , Paniculitis Peritoneal/patología , Tomografía Computarizada por Rayos XRESUMEN
We describe a case of facial skin infection and sinusitis caused by Mycobacterium marseillense in an immunocompetent woman in China in 2018. The infection was cleared with clarithromycin, moxifloxacin, and amikacin. Antimicrobial drug treatments could not be predicted by genetic analyses; further genetic characterization would be required to do so.
Asunto(s)
Infecciones por Mycobacterium/epidemiología , Mycobacterium , Enfermedades Cutáneas Bacterianas/epidemiología , China/epidemiología , Cara , Femenino , Humanos , Persona de Mediana Edad , Mycobacterium/genética , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Filogenia , ARN Ribosómico 16S/genética , Piel/microbiología , Piel/patología , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/patologíaRESUMEN
The implications of TLR-2 mediated alterations in cytosolic-Ca2+((Ca2+)c) levels in M. smegmatis infections is not well known. Using headkidney macrophages (HKM) from Clarias gariepinus, we observed TLR-2 signalling is required in the phagocytosis of M. smegmatis. M. smegmatis induced caspase-dependent HKM apoptosis in MOI, time and growth-phase dependent manner. RNAi and inhibitor studies demonstrated critical role of TLR-2 in eliciting (Ca2+)c-surge and c-Src-PI3K-PLC axis playing an intermediary role in the process. The (Ca2+)c-surge triggered downstream ER-stress and superoxide (O2-) generation. The cross-talk between ER-stress and O2- amplified TNF-α production, which led to HKM apoptosis and bacterial clearance. Release of nitric oxide (NO) was also observed and silencing the NOS2-NO axis enhanced intracellular bacterial survival and attenuated caspase activity. Pre-treatment with diphenyleneidonium chloride inhibited NO production implicating O2--NO axis imperative in M. smegmatis-induced HKM apoptosis. NO positively impacted CHOP expression and TNF-α production in infected HKM. We conclude that, TLR-2 induced (Ca2+)c-surge and ensuing cross-talk between ER-stress and O2- potentiates HKM pathology by amplifying pro-inflammatory TNF-α production. Moreover, the pro-oxidant environment triggers NO release which prolonged ER-stress and TNF-α production, culminating in HKM apoptosis and bacterial clearance. Together, our study suggests HKM an alternate model to study macrophage-mycobacteria interactions.
Asunto(s)
Calcio/metabolismo , Bagres/microbiología , Estrés del Retículo Endoplásmico , Macrófagos/microbiología , Mycobacterium smegmatis/fisiología , Óxido Nítrico/metabolismo , Superóxidos/metabolismo , Receptor Toll-Like 2/metabolismo , Animales , Apoptosis , Citosol/metabolismo , Riñón Cefálico/patología , Inmunidad Innata , Infecciones por Mycobacterium/microbiología , Infecciones por Mycobacterium/patología , Fagocitosis , Transducción de Señal , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Nontuberculous mycobacteria (NTM) infect children with increasing frequency worldwide. Using blood and lymph node tissue from children with NTM lymphadenitis, and uninfected lymph node tissue from community controls, we evaluated helper T (TH) cells in functional assays of TH1/TH17 differentiation and measured the concentration of their associated cytokines at the site of infection. Circulating TH cells from infected children were attenuated in their TH1/TH17 differentiation capacity and expressed less interferon γ and interleukin 17 after polyclonal stimulation. Similar differences were observed at the site of infection, where most cytokine concentrations were unchanged relative to controls. Our data are consistent with a model wherein TH1/TH17 differentiation is attenuated in NTM-infected children.
Asunto(s)
Diferenciación Celular , Infecciones por Mycobacterium/patología , Micobacterias no Tuberculosas/inmunología , Células TH1/inmunología , Células Th17/inmunología , Adolescente , Sangre/inmunología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Interferón gamma/análisis , Interleucina-17/análisis , Ganglios Linfáticos/inmunología , Masculino , Infecciones por Mycobacterium/inmunologíaRESUMEN
Cardiovascular disease (CVD) is the leading cause of death in industrialized nations and an emerging health problem in the developing world. Systemic inflammatory processes associated with alterations in lipid metabolism are a major contributing factor that mediates the development of CVDs, especially atherosclerosis. Therefore, the pathways promoting alterations in lipid metabolism and the interplay between varying cellular types, signaling agents, and effector molecules have been well-studied. Mycobacterial species are the causative agents of various infectious diseases in both humans and animals. Modulation of host lipid metabolism by mycobacteria plays a prominent role in its survival strategy within the host as well as in disease pathogenesis. However, there are still several knowledge gaps in the mechanistic understanding of how mycobacteria can alter host lipid metabolism. Considering the in-depth research available in the area of cardiovascular research, this review presents an overview of the parallel areas of research in host lipid-mediated immunological changes that might be extrapolated and explored to understand the underlying basis of mycobacterial pathogenesis.