RESUMO
OBJECTIVE: To describe health burden and health service utilization from the prenatal period to 1 year postpartum among women with births covered by Texas Medicaid, focusing on the major contributors to maternal mortality after 60 days postpartum in Texas. METHODS: We analyzed diagnoses and health service utilization during the prenatal, early postpartum (5-60 days postpartum), and late postpartum (> 60 days to 1 year postpartum) periods, using administrative medical claims data for women ages 18-44 years with a Medicaid-paid delivery in 2017 residing in selected regions in Texas (n = 49,302). RESULTS: Overall, 12.6% and 17.5% of women had diagnoses of cardiovascular/coronary conditions and substance use disorder, respectively. Mental health conditions affected 30% of women, with anxiety (47.1%) and depression (34.3%) accounting for the greatest proportion of diagnosed mental health conditions. The prevalence of these conditions was higher during the late (19.4%) versus early (9.9%) postpartum period. About 47.8% of women had other chronic health conditions, including obesity, diabetes mellitus, and hypertension. Among women with the selected health conditions, utilization of any health services was higher during the prenatal period compared to early and late postpartum periods (e.g., any mental health service utilization: prenatal period (57.4%) versus early postpartum (26.9%) and late postpartum (25.5%) periods). However, among women with the selected health conditions, there was a high utilization of emergency room services during the late postpartum period [e.g., emergency room service utilization among those with mental health conditions: prenatal period (35.6%); postpartum period: early (5.5%) and late (30.1%)]. CONCLUSIONS FOR PRACTICE: Increasing access to the full range of recommended services during the prenatal period through 1 year postpartum has potential to help improve vulnerable women's birth outcomes.
Assuntos
Medicaid , Serviços de Saúde Mental , Adolescente , Adulto , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Período Pós-Parto , Gravidez , Texas/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Stark differences in the infant mortality rate (IMR) exist by geography in Texas. The Healthy Families initiative sought to understand how evidence-informed practices implemented in the community can improve pregnancy-related outcomes in 2 counties in Texas with a high prevalence of maternal chronic conditions. The objective of this study was to examine associations between maternal risk factors and infant deaths to inform strategies to improve outcomes. METHODS: Two counties with high prevalence of maternal chronic conditions were selected as Healthy Families sites: one with lower prenatal care usage than other counties in the state but an IMR lower than Texas, and the other with a higher IMR among minority racial and ethnic groups compared with other women in the county and Texas overall. Cohort-linked birth and infant death records from 2011 through 2015 provided by the Texas Department of State Health Services were analyzed by using logistic regression to examine associations of maternal sociodemographic and pregnancy risk factors with infant death. The data were mapped at the zip code level. Analyses were limited to births to women aged 15 to 49 years who resided in Texas from 2011 through 2015 (n = 1,942,899 births). RESULTS: The Texas IMR was 5.4 per 1,000 live births, compared with 4.6 and 7.5 per 1,000 live births for Hidalgo and Smith counties, respectively. Congenital malformations were the leading cause of infant death in both counties for infants born in 2015, which was similar to Texas overall. In both counties, maternal marital status, education, multiple gestation, and cesarean delivery were significantly associated with infant mortality. Wide zip code-level variations in IMR and maternal risk factors were observed in both counties. CONCLUSION: Variations in IMR and key maternal risk factors observed at the zip code level helped drive local strategies to maximize outreach of services to disproportionately affected communities.
Assuntos
Mortalidade Infantil , Cuidado Pré-Natal , Criança , Feminino , Humanos , Lactente , Gravidez , Resultado da Gravidez , Fatores de Risco , Texas/epidemiologiaRESUMO
BACKGROUND: Severe maternal morbidity (SMM) prevalence was 194.0 per 10 000 deliveries in Texas in 2015. Chronic, behavioral, and pregnancy-induced conditions, as captured by a maternal comorbidity index, increase the risk for delivery-related morbidity and mortality. The objective of the study was to examine the association between maternal comorbidity index and SMM among delivery hospitalizations in Texas. METHODS: Delivery-related hospitalizations among Texan women aged 15-49 years were identified using the 2011-2014 Texas all-payer inpatient hospitalization public use data files (n = 1 434 441). The primary outcome of interest was SMM, based on the Alliance for Innovation on Maternal Health's coding scheme. The exposure of interest was a maternal comorbidity index. Multivariable logistic regression model was used to examine the association between maternal comorbidity index and SMM. RESULTS: SMM prevalence remained consistent between 2011 and 2014 (196.0-197.0 per 10 000 deliveries, P > .05; n = 1 434 441). Nearly 40% of delivery-related hospitalizations had a maternal comorbidity index of at least 1, and the proportion of deliveries in the highest risk category of comorbidity index (≥5) increased by 12.0% from 2011 to 2014. SMM prevalence was highest among the youngest and oldest age groups. With each unit increase in maternal comorbidity index, the odds of SMM increase was 1.43 (95% CI 1.42-1.43). CONCLUSIONS: Maternal comorbidity index is associated with SMM; however, the low predictive power of the model suggests that other, unmeasured factors may influence SMM in Texas. These findings highlight a need to understand broader contextual factors (practitioner, facility, systems of care, and community) that may be associated with SMM to reduce maternal morbidity and mortality in Texas.
Assuntos
Mortalidade Materna/tendências , Morbidade/tendências , Complicações na Gravidez/mortalidade , Adolescente , Adulto , Comorbidade , Estudos Transversais , Feminino , Hospitalização , Humanos , Modelos Logísticos , Idade Materna , Pessoa de Meia-Idade , Análise Multivariada , Gravidez , Complicações na Gravidez/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Texas/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Cesarean delivery accounts for over one-third of the ~400 000 annual births in Texas, with first-time cesarean accounting for 20% of the overall cesareans. We examined associations of maternal medical comorbidities with cesarean delivery among nulliparous, term, singleton, vertex (NTSV) deliveries in Texas. METHODS: Nulliparous, term, singleton, vertex deliveries to women aged 15-49 years were identified using the 2015 Texas birth file (Center for Health Statistics, Texas Department of State Health Services). A risk factor index was constructed (score range 0-4), including preexisting/gestational diabetes mellitus, preexisting/gestational hypertension/eclampsia, infertility treatment, smoking during pregnancy, and prepregnancy overweight/obesity, and categorized as 0, 1, 2, and 3+ based on the number of risk factors present. Multivariable logistic regression analyses were conducted to examine associations between the categorized risk factor index and cesarean delivery, overall and by maternal race and ethnicity. RESULTS: Among the 114 535 NTSV deliveries in Texas in 2015, 27.2% were by cesarean. The most prevalent maternal risk among all deliveries was prepregnancy overweight/obesity (42.4%). The odds of cesarean delivery increased significantly with increasing number of risk factors [one risk factor: 1.72 (95% CI 1.67-1.78); two risk factors: 2.58 (95% CI 2.46-2.71); and three or more risk factors: 3.91 (95% CI 3.45-4.44)]. DISCUSSION: In Texas in 2015, nearly half of NTSV deliveries had at least one maternal risk factor and the odds of cesarean delivery were significantly elevated for women with a higher risk index score. The findings from this study highlight the need for intervening during the preconception and interconception period as intrapartum care practices have an important influence on birth outcomes.
Assuntos
Cesárea/estatística & dados numéricos , Sobrepeso/epidemiologia , Adolescente , Adulto , Declaração de Nascimento , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Paridade , Gravidez , Fatores de Risco , Nascimento a Termo , Texas/epidemiologia , Adulto JovemRESUMO
Health care personnel (HCP) caring for patients with Ebola virus disease (EVD) are at increased risk for infection with the virus. In 2014, a Texas hospital became the first U.S. community hospital to care for a patient with EVD; 2 nurses were infected while providing care. This article describes infection control measures developed to strengthen the hospital's capacity to safely diagnose and treat patients with EVD. After admission of the first patient with EVD, a multidisciplinary team from the Centers for Disease Control and Prevention (CDC) joined the hospital's infection preventionists to implement a system of occupational safety and health controls for direct patient care, handling of clinical specimens, and managing regulated medical waste. Existing engineering and administrative controls were strengthened. The personal protective equipment (PPE) ensemble was standardized, HCP were trained on donning and doffing PPE, and a system of trained observers supervising PPE donning and doffing was implemented. Caring for patients with EVD placed substantial demands on a community hospital. The experiences of the authors and others informed national policies for the care of patients with EVD and protection of HCP, including new guidance for PPE, a rapid system for deploying CDC staff to assist hospitals ("Ebola Response Team"), and a framework for a tiered approach to hospital preparedness. The designation of regional Ebola treatment centers and the establishment of the National Ebola Training and Education Center address the need for HCP to be prepared to safely care for patients with EVD and other high-consequence emerging infectious diseases.
RESUMO
BACKGROUND: Following hospitalization of the first patient with Ebola virus disease diagnosed in the United States on 28 September 2014, contact tracing methods for Ebola were implemented. OBJECTIVE: To identify, risk-stratify, and monitor contacts of patients with Ebola. DESIGN: Descriptive investigation. SETTING: Dallas County, Texas, September to November 2014. PARTICIPANTS: Contacts of symptomatic patients with Ebola. MEASUREMENTS: Contact identification, exposure risk classification, symptom development, and Ebola. RESULTS: The investigation identified 179 contacts, 139 of whom were contacts of the index patient. Of 112 health care personnel (HCP) contacts of the index case, 22 (20%) had known unprotected exposures and 37 (30%) did not have known unprotected exposures but interacted with a patient or contaminated environment on multiple days. Transmission was confirmed in 2 HCP who had substantial interaction with the patient while wearing personal protective equipment. These HCP had 40 additional contacts. Of 20 community contacts of the index patient or the 2 HCP, 4 had high-risk exposures. Movement restrictions were extended to all 179 contacts; 7 contacts were quarantined. Seven percent (14 of 179) of contacts (1 community contact and 13 health care contacts) were evaluated for Ebola during the monitoring period. LIMITATION: Data cannot be used to infer whether in-person direct active monitoring is superior to active monitoring alone for early detection of symptomatic contacts. CONCLUSION: Contact tracing and monitoring approaches for Ebola were adapted to account for the evolving understanding of risks for unrecognized HCP transmission. HCP contacts in the United States without known unprotected exposures should be considered as having a low (but not zero) risk for Ebola and should be actively monitored for symptoms. Core challenges of contact tracing for high-consequence communicable diseases included rapid comprehensive contact identification, large-scale direct active monitoring of contacts, large-scale application of movement restrictions, and necessity of humanitarian support services to meet nonclinical needs of contacts. PRIMARY FUNDING SOURCE: None.
Assuntos
Busca de Comunicante , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/epidemiologia , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Recursos Humanos de Enfermagem Hospitalar , Quarentena , Medição de Risco , Texas/epidemiologiaRESUMO
Since March 10, 2014, Guinea, Liberia, and Sierra Leone have experienced the largest known Ebola virus disease (Ebola) epidemic with approximately 13,000 persons infected as of October 28, 2014. Before September 25, 2014, only four patients with Ebola had been treated in the United States; all of these patients had been diagnosed in West Africa and medically evacuated to the United States for care.
Assuntos
Busca de Comunicante , Ebolavirus/isolamento & purificação , Epidemias/prevenção & controle , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/prevenção & controle , Vigilância da População , Análise por Conglomerados , Feminino , Doença pelo Vírus Ebola/epidemiologia , Humanos , Libéria/epidemiologia , Masculino , Pessoa de Meia-Idade , Texas/epidemiologia , ViagemRESUMO
BACKGROUND: While the Texas infant mortality rate (IMR) is below the Healthy People 2020 objective (5.7 per 1,000 live births), stark differences in IMR are seen across Texas communities. Health indicators for the state suggest important missed opportunities for improving maternal and infant outcomes. The Healthy Families initiative was a collaboration between a Texas state agency, community partners, and academic institutions to understand how evidence-based interventions could be identified, adapted, and implemented to address community priorities and reduce disparities in pregnancy outcomes. METHOD: The Healthy Families initiative included two Texas counties, one with low utilization of prenatal care and one with persistent disparities in infant mortality. The model served to (1) identify community factors influencing IMR and maternal morbidity through stakeholder engagement and secondary data, (2) build community capacity to link pregnant women with existing and newly developed services, and (3) develop partnerships within the community and clinics to improve access to and sustainability of services. RESULTS: A community-based participatory approach focused on stakeholder engagement was used to identify, design, and adapt strategies to address community-identified priorities. CONCLUSIONS: The Healthy Families initiative is a unique state-community-academic partnership aimed at improving pregnancy outcomes in vulnerable communities, with a focus on promotion of capacity building, maintenance, and sustainability of maternal and infant health programs.
Assuntos
Saúde da Família , Resultado da Gravidez , Pesquisa Participativa Baseada na Comunidade , Feminino , Humanos , Lactente , Mortalidade Infantil , Gravidez , Cuidado Pré-Natal , TexasRESUMO
BACKGROUND: Minority race/ethnicity, low socioeconomic status, and lack of established paternity have been identified in previous research as risk factors for child maltreatment. However, given vastly different patterns of income distribution, single parenting and co-parenting across racial and ethnic populations, it is difficult to know which of these factors contribute most to maltreatment risk. OBJECTIVE: The current study explores whether the odds of maltreatment differ across race/ethnicity when paternity is not established at birth after controlling for maternal socioeconomic status. METHODS: Using merged birth certificate and child protective services records for children born between 2009 and 2011 in Texas (N = 1,175,804), we conducted multiple logistic regression analyses testing the main effects of maternal race and lack of established paternity, as well as the interaction of the two, on substantiated maltreatment. RESULTS: Results show that children of black mothers were less likely to have established paternity and more likely to experience maltreatment compared with other groups. However, the odds of maltreatment were lower for children of black mothers without established paternity compared to children of white mothers without established paternity (OR = .71, 95% CI [0.67,0.75]). Alternatively, the odds of maltreatment were higher when paternity was not established at birth for Hispanic mothers (OR = 1.13, 95% CI [1.08,1.18]) and mothers of other race/ethnicities (OR = 1.35, 95% CI [1.11,1.65]) compared to white mothers. CONCLUSION: Research and prevention programming must consider that the processes and pathways linking paternity establishment and maltreatment may differ within and between racial/ethnic groups.
Assuntos
Maus-Tratos Infantis/etnologia , Paternidade , Adulto , Negro ou Afro-Americano , Criança , Serviços de Proteção Infantil , Relações Familiares , Feminino , Hispânico ou Latino , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Mães , Fatores de Risco , TexasRESUMO
BACKGROUND: Induction of labor (IOL) is increasingly common in the United States, yet characteristics associated with IOL among primiparous women delivering at term are not well understood. MATERIALS AND METHODS: Data from the Listening to Mothers III study, a survey of women aged 18-45 with singleton deliveries in U.S. hospitals in 2011-2012, were utilized. Weighted logistic regression models examined predictors of IOL among 924 primiparous women with term deliveries. Associations of maternal characteristics with delivery route (cesarean and vaginal delivery) were examined among primiparous women induced at term. RESULTS: Four hundred twenty-three (45.8%) primiparous women with term deliveries underwent IOL; subjective reasons were reported by 53% of induced women. Women who were married (odds ratios [OR] = 1.8, 95% confidence intervals [CI] 1.2-2.9), felt pressure from a provider for IOL (OR = 3.5, 95% CI 2.0-6.2), and whose provider was concerned about the size of the baby (OR = 1.9, 95% CI 1.2-2.9) were significantly more likely to undergo IOL. Nearly 30% of primiparous women who underwent IOL at term had a cesarean delivery (CD). Among the induced women, those who were overweight/obese (OR = 4.9, 95% CI 2.5-10.0), felt pressure from a provider for CD (OR = 8.6, 95% CI 3.5-21.2), and whose provider suspected the baby might be getting large near end of pregnancy (OR = 2.7, 95% CI 1.1-7.0) were significantly more likely to have CD. CONCLUSIONS: In this study, nearly half of the primiparous women with term deliveries underwent IOL, with a sizeable proportion reporting subjective reasons for induction. A better understanding of the characteristics associated with IOL at term may help reduce unnecessary interventions and, ultimately, primary CD.
Assuntos
Cesárea/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Paridade , Nascimento a Termo , Adolescente , Adulto , Estudos Transversais , Feminino , Peso Fetal , Idade Gestacional , Humanos , Trabalho de Parto , Pessoa de Meia-Idade , Gravidez , Fatores Socioeconômicos , Adulto JovemAssuntos
COVID-19 , SARS-CoV-2 , Adolescente , Anticorpos Antivirais , Criança , Hospitalização , Humanos , Testes ImunológicosRESUMO
To characterize the manifestations of coinfection with M. tuberculosis and SIV infection, we studied 12 SIV-infected rhesus monkeys, six of which were infected intrabronchially with a low dose of Mycobacterium tuberculosis H37Rv. In the six coinfected animals, M. tuberculosis antigen-stimulated lung and blood cells produced high concentrations of IFN-gamma but not IL-4 8-16 weeks after infection. Of the three coinfected animals with high levels of plasma viremia, two developed disseminated tuberculosis and the other died of bacterial peritonitis. Of three coinfected animals with moderate levels of plasma viremia, two had no clinical or radiographic evidence of tuberculosis or progressive SIV infection for 6 months after infection. At neuropsy, pulmonary granulomata were observed and acid-fast organisms or M. tuberculosis were present. These clinical, immunologic and pathologic findings are consistent with those in humans with latent tuberculosis infection (LTBI), and suggest that a model of LTBI in SIV-infected primates can be developed. Such a model will permit delineation of the immunologic and microbial factors that characterize LTBI in HIV-infected persons.
Assuntos
Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Tuberculose Pulmonar/complicações , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Regulação da Expressão Gênica , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-4/biossíntese , Interleucina-4/genética , Leucócitos Mononucleares/metabolismo , Pulmão/patologia , Macaca mulatta , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Tuberculoma/patologia , Tuberculose Miliar/complicações , Tuberculose Miliar/imunologia , Tuberculose Miliar/patologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Carga Viral , Viremia/complicações , Redução de PesoRESUMO
In the past 5 years, there have been significant advances in the understanding of the pathogenesis of TB in people infected with HIV and in the approach to diagnosis, treatment, and prevention in patients with HIV. Nucleic acid amplification tests and restriction fragment length polymorphism can contribute to the clinical management of TB patients. New guidelines are available for the treatment of active and latent TB infection in patients with HIV.
Assuntos
Infecções por HIV/complicações , Tuberculose/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose/tratamento farmacológicoRESUMO
Prior reports have suggested that CD14 mediates uptake of Mycobacterium tuberculosis into porcine alveolar macrophages and human fetal microglia, but the contribution of CD14 to cell entry in human macrophages has not been studied. To address this question, we used flow cytometry to quantify uptake by human monocytes and alveolar macrophages of M. tuberculosis expressing green fluorescent protein. Neutralizing anti-CD14 antibodies did not affect bacillary uptake and the efficiency of bacillary entry was similar in THP-1 cells expressing low and high levels of CD14. However, most internalized bacteria were found in CD14+ but not in CD14- monocytes because M. tuberculosis infection upregulated CD14 expression. We conclude that: (1) CD14 does not mediate cellular entry by M. tuberculosis; (2) M. tuberculosis infection upregulates CD14 expression on mononuclear phagocytes, and this may facilitate the pathogen's capacity to modulate the immune response.
Assuntos
Receptores de Lipopolissacarídeos/imunologia , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Células Cultivadas , Citometria de Fluxo , Proteínas de Fluorescência Verde , Humanos , Separação Imunomagnética , Proteínas Luminescentes/metabolismo , Macrófagos Alveolares/imunologia , Microscopia de Fluorescência , Tuberculose Pulmonar/microbiologiaRESUMO
The mobile insertion sequence, IS6110, is an important marker in tracking of Mycobacterium tuberculosis strains. Here, we demonstrate that IS6110 can upregulate downstream genes through an outward-directed promoter in its 3' end, thus adding to the significance of this element. Promoter activity was orientation dependent and was localized within a 110 bp fragment adjacent to the right terminal inverted repeat. Transcripts from this promoter, named OP6110, begin approximately 85 bp upstream of the 3' end of IS6110. Use of green fluorescent protein (GFP) expression constructs showed that OP6110 was upregulated in M. tuberculosis during growth in human monocytes and in late growth phases in broth. Analysis of natural insertion sites in M. tuberculosis showed that IS6110 upregulated expression of several downstream genes during growth in human monocytes, including Rv2280 in H37Rv and the PE-PGRS gene, Rv1468c, in the clinical strain 210, which is a member of the Beijing family. Transcription between IS6110 and downstream genes was confirmed by reverse transcription polymerase chain reaction. The ability to activate genes during infection suggests that IS6110 has the potential to influence growth characteristics of different strains, and indicates another mechanism by which IS6110 can impact M. tuberculosis evolution.
Assuntos
Elementos de DNA Transponíveis , Monócitos/microbiologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiologia , Regiões Promotoras Genéticas , Fusão Gênica Artificial , Linhagem Celular , Regulação Bacteriana da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde , Humanos , Proteínas Luminescentes/metabolismo , Mycobacterium tuberculosis/crescimento & desenvolvimento , RNA Bacteriano/análise , RNA Bacteriano/isolamento & purificação , RNA Mensageiro/análise , RNA Mensageiro/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sequências Repetidas Terminais , Sítio de Iniciação de Transcrição , Regulação para CimaRESUMO
Mycobacterium tuberculosis survives in macrophages in the face of acquired CD4(+) T-cell immunity, which controls but does not eliminate the organism. Gamma interferon (IFN-gamma) has a central role in host defenses against M. tuberculosis by activating macrophages and regulating major histocompatibility complex class II (MHC-II) antigen (Ag) processing. M. tuberculosis interferes with IFN-gamma receptor (IFN-gamma R) signaling in macrophages, but the molecules responsible for this inhibition are poorly defined. This study determined that the 19-kDa lipoprotein from M. tuberculosis inhibits IFN-gamma-regulated HLA-DR protein and mRNA expression in human macrophages. Inhibition of HLA-DR expression was associated with decreased processing and presentation of soluble protein Ags and M. tuberculosis bacilli to MHC-II-restricted T cells. Inhibition of HLA-DR required prolonged exposure to 19-kDa lipoprotein and was blocked with a monoclonal antibody specific for Toll-like receptor 2 (TLR-2). The 19-kDa lipoprotein also inhibited IFN-gamma-induced expression of Fc gamma RI. Thus, M. tuberculosis, through 19-kDa lipoprotein activation of TLR-2, inhibits IFN-gamma R signaling in human macrophages, resulting in decreased MHC-II Ag processing and recognition by MHC-II-restricted CD4 T cells. These findings provide a mechanism for M. tuberculosis persistence in macrophages.
Assuntos
Proteínas de Bactérias/toxicidade , Lipoproteínas/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Animais , Anticorpos Monoclonais/farmacologia , Apresentação de Antígeno/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sequência de Bases , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Hibridomas/imunologia , Interferon gama/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo , Receptores de Interferon/efeitos dos fármacos , Receptores de Interferon/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like , Receptores Toll-Like , Receptor de Interferon gamaRESUMO
We used human tuberculosis as a model to investigate the role of NK cytotoxic mechanisms in the immune response to intracellular infection. Freshly isolated NK cells and NK cell lines from healthy donors lysed Mycobacterium tuberculosis-infected monocytes to a greater extent than uninfected monocytes. Lysis of infected monocytes was associated with increased expression of mRNA for the NKp46 receptor, but not the NKp44 receptor. Antisera to NKp46 markedly inhibited lysis of infected monocytes. NK cell-mediated lysis was not due to reduced expression of MHC class I molecules on the surface of infected monocytes or to enhanced production of IL-18 or IFN-gamma. NK cell lytic activity against M. tuberculosis-infected monocytes and NKp46 mRNA expression were reduced in tuberculosis patients with ineffective immunity to M. tuberculosis compared with findings in healthy donors. These observations suggest that 1) the NKp46 receptor participates in NK cell-mediated lysis of cells infected with an intracellular pathogen, and 2) the reduced functional capacity of NK cells is associated with severe manifestations of infectious disease.
Assuntos
Citotoxicidade Imunológica , Líquido Intracelular/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/imunologia , Mycobacterium tuberculosis/imunologia , Fagócitos/imunologia , Receptores Imunológicos/fisiologia , Linhagem Celular , Sobrevivência Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Citocinas/biossíntese , Citocinas/imunologia , Citotoxicidade Imunológica/imunologia , Antígenos de Histocompatibilidade Classe I/biossíntese , Humanos , Soros Imunes/farmacologia , Líquido Intracelular/microbiologia , Células K562 , Células Matadoras Naturais/citologia , Leucócitos Mononucleares/microbiologia , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/microbiologia , Receptor 1 Desencadeador da Citotoxicidade Natural , Receptor 2 Desencadeador da Citotoxicidade Natural , Fagócitos/microbiologia , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/biossíntese , Receptores Imunológicos/biossíntese , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Tuberculose/imunologiaRESUMO
Several recent publications have suggested that oligo(dT) can prime reverse transcription of several mycobacterial mRNAs. To determine if this is the case for most Mycobacterium tuberculosis mRNA species, reverse transcription reactions of M. tuberculosis RNA were primed with oligo(dT) or with other primers that did not target polyadenylylated sequences, and the resultant cDNA product was evaluated. Priming with oligo(dT) yielded more cDNA than priming with an arbitrary primer for only 1 of 12 unrelated M. tuberculosis genes, as measured by competitive PCR. Priming with oligo(dT) yielded cDNA for only 30% of the genes primed for by 37 M. tuberculosis genome-directed oligonucleotides, as assessed by hybridization of cDNA with an M. tuberculosis microarray. These data demonstrate that priming of reverse transcription of mycobacterial mRNA with oligo(dT) does not yield representative samples of cDNA.
Assuntos
DNA Complementar/genética , Mycobacterium tuberculosis/genética , Oligodesoxirribonucleotídeos/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Primers do DNA/genética , DNA Complementar/biossíntese , Regulação Bacteriana da Expressão Gênica , Mycobacterium tuberculosis/enzimologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/química , RNA Mensageiro/genética , Transcrição GênicaRESUMO
The ability of Mycobacterium tuberculosis to grow in macrophages is central to its pathogenicity. We found previously that the widespread 210 strain of M. tuberculosis grew more rapidly than other strains in human macrophages. Because principal sigma factors influence virulence in some bacteria, we analysed mRNA expression of the principal sigma factor, sigA, in M. tuberculosis isolates during growth in human macrophages. Isolates of the 210 strain had higher sigA mRNA levels and higher intracellular growth rates, compared with other clinical strains and the laboratory strain H37Rv. SigA was also upregulated in the 210 isolate TB294 during growth in macrophages, compared with growth in broth. In contrast, H37Rv sigA mRNA levels did not change under these conditions. Overexpression of sigA enhanced growth of recombinant M. tuberculosis in macrophages and in lungs of mice after aerosol infection, whereas recombinant strains expressing antisense transcripts to sigA showed decreased growth in both models. In the presence of superoxide, sense sigA transformants showed greater resistance than vector controls, and the antisense sigA transformant did not grow. We conclude that M. tuberculosis sigA modulates the expression of genes that contribute to virulence, enhancing growth in human macrophages and during the early phases of pulmonary infection in vivo. This effect may be mediated in part by increased resistance to reactive oxygen intermediates.