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Intradermal injection of anti-immunoglobulin E (IgE) antibodies in dogs grossly and histologically resemble naturally occurring atopic dermatitis (AD). However, the activated inflammatory and pruritic pathways have not been characterized. The objectives of this study were to characterize the inflammatory transcriptome of experimental acute canine IgE-induced lesions and to determine how these correlate to the transcriptome of naturally occurring human and canine acute atopic dermatitis. Biopsies were collected at 6 and 24 h after intradermal injections of anticanine-IgE antibodies to eight healthy male castrated Beagles; healthy and saline-injected skin served as controls. We extracted total RNA from skin biopsies and analyzed transcriptome using RNA-sequencing. Gene expressions of IgE-induced biopsies were compared to that of controls from the same subject (1.5-fold change, p-adjusted value ≤ 0.05). Acute IgE-mediated lesions had a significant upregulation of pro-inflammatory (e.g., LTB, IL-1B, PTX3, CCL2, IL6, IL8, IL18), T helper-(Th)1/IFNγ signal (e.g., STAT-1, OASL, MX-1, CXCL10, IL-12A) and Th2 (e.g., IL4R, IL5, IL13, IL33 and POSTN) genes, as well as Th2 chemokines (CCL17, CCL24). Pathway analysis revealed strong significant upregulation of JAK-STAT, histamine, IL-4 and IL13 signaling. Spearman correlation coefficient for the shared DEGs between canine anti-canine-IgE and human AD samples revealed a significant moderate positive correlation for anti-canine-IgE 6-h samples (r = 0.53) and 24-h samples (r = 0.47). In conclusion, acute canine IgE-mediated skin lesions exhibit a multipolar immunological axis upregulation (Th1, Th2 and Th17) in healthy dogs, resembling acute spontaneous human AD lesions.
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Eclampsia is one of the leading causes of maternal death worldwide. The purpose of our study was to determine maternal and perinatal prognosis of eclampsia at the Timbuktu Hospital in Mali. We conducted a descriptive, retrospective study of patients with eclampsia during pregnancy or delivery at the Timbuktu Hospital from January 1, 2013 to December 31, 2017. Out of 4.951 deliveries, 116 were marked by eclampsia, reflecting an overall rate of 2.3%. These patients were mainly women younger than 26 years (85.3%), primiparous (81%), admitted on average 8 hours after the first crisis. Cesarean section was performed in 77.6% of cases. Magnesium sulphate was used in 75% of cases. Maternal and perinatal mortality accounted for 4.3% and 21.5%, respectively. Poor maternal prognosis factor was Glasgow score ≤ 8 on admission (p: 0.004). Poor perinatal prognosis factors were to be resident outside the city of Timbuktu (p: 0.000), the absence of antenatal consultation (p: 0.020) and vaginal delivery (p: 0.012). Thus, improving maternal and perinatal prognosis requires proper monitoring of pregnancies and reduction of delays in accessing adequate care.
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Cesárea/estadística & datos numéricos , Eclampsia/epidemiología , Sulfato de Magnesio/administración & dosificación , Resultado del Embarazo , Adolescente , Adulto , Femenino , Humanos , Recién Nacido , Malí , Mortalidad Materna , Mortalidad Perinatal , Embarazo , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Many headache smartphone applications (apps) are commercially available. A Modified Delphi Study aimed to determine specialists' expectations of what a headache app should entail but consumer expectations of headache apps have not been evaluated extensively. OBJECTIVE: To evaluate publicly available reviews of headache apps to understand app features that motivate the consumers to use apps. METHODS: The Google Play and Apple App Stores were systematically searched for headache/migraine diary apps with 10+ consumer reviews. A maximum of 300 "Most Helpful" reviews for each app were extracted. Four coders coded reviews and resolved discrepancies. Themes and subthemes were created based on codes used 5+ times. RESULTS: About 15 apps met the study criteria (9 Android, 6 IOS). 945 reviews were coded. Four themes emerged: (1) App allows users to track headache characteristics, potential triggers, and treatments; (2) App usability; (3) Personalization and features to assess trends in data are key motivators for app use; (4) Ease with exportation and viewing data is critical. DISCUSSION: A user-centered design with the ability to (1) customize key features including headache characteristics, potential triggers, and treatments, (2) assess trends in data, and (3) view and export data would best optimize headache smartphone applications based on consumer preference.
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Cefalea , Trastornos Migrañosos , Aplicaciones Móviles , Prioridad del Paciente , Interfaz Usuario-Computador , Adulto , Técnica Delphi , Cefalea/diagnóstico , Cefalea/terapia , Humanos , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/terapia , Investigación Cualitativa , Teléfono InteligenteRESUMEN
Perinatal lambs are increasingly appreciated as a model to study respiratory infections of premature and newborn human infants. To explore the relationship between developmental age and immunological competence in the respiratory tract, the basal levels of expression of genes involved in innate and adaptive immune functions in the lung were examined in pre-term lambs (115 days and 130 days), at birth (145 days) and post-partum (15 days and 3 years old). Our results show that innate immune genes (TLRs-3, -4, -7, -8; SP-A, SP-D, and SBD1) were differentially expressed through development; cytokines (IFN-γ, IL-6, TNF-α) and chemokines (IL-8, MCP-1) were low during gestation and post-partum but maximal at birth; genes involved in adaptive immunity (PD-1, PD-L1, TGF-ß) were present in pre-term and newborn lung, but were lower in adult lung. The results suggest that pre-term and neonatal lambs may be able to mount an immune response following infection, but that the response may not be optimal. Our studies provide an important set of comparative data on the ontogeny of lung immunity in sheep and set a framework for studies on age-dependent susceptibility to respiratory pathogens.
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Pulmón/inmunología , Modelos Animales , Infecciones del Sistema Respiratorio/inmunología , Ovinos/inmunología , Inmunidad Adaptativa/genética , Animales , Animales Recién Nacidos , Bovinos , Citocinas/genética , Citocinas/inmunología , Citocinas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Edad Gestacional , Humanos , Inmunidad Innata/genética , Proteínas Asociadas a Surfactante Pulmonar/genética , Proteínas Asociadas a Surfactante Pulmonar/inmunología , Proteínas Asociadas a Surfactante Pulmonar/metabolismo , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/inmunología , Receptor Toll-Like 3/metabolismoRESUMEN
INTRODUCTION: Factors explaining the greater susceptibility of preterm infants to severe lower respiratory infections with respiratory syncytial virus (RSV) remain poorly understood. Fetal/newborn lambs are increasingly appreciated as a model to study key elements of RSV infection in newborn infants due to similarities in lung alveolar development, immune response, and susceptibility to RSV. Previously, our laboratory demonstrated that preterm lambs had elevated viral antigen and developed more severe lesions compared to full-term lambs at seven days post-infection. Here, we compared the pathogenesis and immunological response to RSV infection in lungs of preterm and full-term lambs. METHODS: Lambs were delivered preterm by Caesarian section or full-term by natural birth, then inoculated with bovine RSV (bRSV) via the intratracheal route. Seven days post-infection, lungs were collected for evaluation of cytokine production, histopathology and cellular infiltration. RESULTS: Compared to full-term lambs, lungs of preterm lambs had a heightened pro-inflammatory response after infection, with significantly increased MCP-1, MIP-1α, IFN-γ, TNF-α and PD-L1 mRNA. RSV infection in the preterm lung was characterized by increased epithelial thickening and periodic acid-Schiff staining, indicative of glycogen retention. Nitric oxide levels were decreased in lungs of infected preterm lambs compared to full-term lambs, indicating alternative macrophage activation. Although infection induced significant neutrophil recruitment into the lungs of preterm lambs, neutrophils produced less myeloperoxidase than those of full-term lambs, suggesting decreased functional activation. CONCLUSIONS: Taken together, our data suggest that increased RSV load and inadequate immune response may contribute to the enhanced disease severity observed in the lungs of preterm lambs.
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Citocinas/metabolismo , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Pulmón/inmunología , Neumonía Viral/inmunología , Nacimiento Prematuro , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/inmunología , Animales , Antígenos CD/genética , Caspasa 3/metabolismo , Cesárea , Quimiocina CCL2/genética , Quimiocina CCL3/genética , Citocinas/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Edad Gestacional , Interferón gamma/genética , Pulmón/patología , Pulmón/virología , Activación de Macrófagos , Activación Neutrófila , Óxido Nítrico/metabolismo , Neumonía Viral/patología , Neumonía Viral/virología , ARN Mensajero/metabolismo , Infecciones por Virus Sincitial Respiratorio/patología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/patogenicidad , Ovinos , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
We investigated the in vitro production of the antimicrobial peptide hepcidin by cells of the innate immune system that harbor Mycobacterium tuberculosis. Stimulation of mouse lung macrophages with M. tuberculosis or IFN-γ + M. tuberculosis induced hepcidin mRNA. In human alveolar A549 epithelial cells, lipoglycans of M. tuberculosis, in particular mannose-capped lipoarabinomannan and phosphatidyl-myo-inositol mannosides, were strong inducers of hepcidin mRNA. In mouse dendritic cells, hepcidin mRNA was increased by subcellular fractions and culture filtrate proteins of M. tuberculosis and by TLR2 and TLR4 agonists, but not by TLR9 agonists, IL-1α, IL-6 or TNF-α. Flow cytometry evaluation of human peripheral blood mononuclear cells demonstrated that CD11c(+) myeloid dendritic cells stimulated with killed M. tuberculosis or live M. bovis BCG produced hepcidin. The production of the antimicrobial peptide hepcidin by cells that interact with M. tuberculosis suggests a host defense mechanism against mycobacteria.
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Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/biosíntesis , Interferón gamma/inmunología , Macrófagos Alveolares/metabolismo , Mycobacterium tuberculosis/metabolismo , ARN Mensajero/inmunología , Tuberculosis Pulmonar/inmunología , Animales , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/farmacología , Femenino , Citometría de Flujo , Hepcidinas , Inmunidad Innata , Macrófagos Alveolares/inmunología , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/metabolismo , Receptor Toll-Like 2/agonistas , Receptor Toll-Like 4/agonistas , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
The effects of ethanol exposure on fetal lungs remain under investigation. Previously, we demonstrated that lambs exposed to ethanol during gestation had impaired expression of pulmonary surfactant protein A, a crucial component of lung immunity. In this study, we investigated the effects of in utero exposure to ethanol on maturation and immunity of the fetal lung. Pregnant ewes were surgically implanted with an abomasal cannula and administered 1g ethanol/kg (n=8) or water (n=8) during the last trimester of pregnancy. Lambs were delivered prematurely or naturally. Neonatal lungs were assessed for maturation markers (hypoxia-inducible factor-1α [HIF-1α], HIF-2α, HIF-3α, vascular endothelial growth factor-A [VEGF-A], VEGFR-1, VEGFR-2, glycogen, and lung protein levels) and immunity (cytokines and chemokines). Preterm animals exposed to ethanol had significantly reduced VEGF-A mRNA (P=.066) and protein levels, HIF-1α (P=.055), HIF-2α (P=.019), VEGFR-1 (P=.088), and VEGFR-2 (P=.067) mRNA levels but no changes in HIF-3α mRNA. No significant changes occurred in full-term animals exposed to ethanol. Glycogen levels were significantly higher in preterm animals exposed to ethanol (P=.006) but not in full-term animals. Ethanol exposure was associated with significantly lower lung protein levels in preterm (P=.03) but not full-term animals. Preterm animals exposed to ethanol had significantly reduced TNF-α (P=.05), IL-10 (P=.03), chemokine (C-C motif) ligand 5 (CCL5) (P=.017), and monocyte chemotactic protein-1 (MCP-1) (P=.0004) mRNA. In full-term animals exposed to ethanol, the immune alterations were either sustained (TNF-α, P=.009; IL-10, P=.03) or returned to near baseline levels (CCL5 and MCP-1). The ethanol-mediated alterations in fetal lung maturation and immunity may explain the increased incidence of respiratory infections in neonates exposed to ethanol in utero.
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Etanol/toxicidad , Madurez de los Órganos Fetales/efectos de los fármacos , Edad Gestacional , Pulmón/efectos de los fármacos , Pulmón/embriología , Ovinos , Animales , Quimiocinas/análisis , Citocinas/análisis , Femenino , Glucógeno/análisis , Factor 1 Inducible por Hipoxia/genética , Pulmón/inmunología , Embarazo , ARN Mensajero/análisis , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children worldwide. The understanding of neonatal RSV pathogenesis depends on using an animal model that reproduces neonatal RSV disease. Previous studies from us and others demonstrated that the neonatal lamb model resembles human neonatal RSV infection. Here, we provide an extensive and detailed characterization of the histopathology, viral load, cellular infiltration, and cytokine production in lungs and tracheobronchial lymph nodes of lambs inoculated with human RSV strain A2 over the course of infection. In the lung, RSV titers were low at day 3 postinfection, increased significantly by day 6, and decreased to baseline levels at day 14. Infection in the lung was associated with an accumulation of macrophages, CD4(+) and CD8(+) T cells, and a transcriptional response of genes involved in inflammation, chemotaxis, and interferon response, characterized by increased IFNγ, IL-8, MCP-1, and PD-L1, and decreased IFNß, IL-10, and TGF-ß. Laser capture microdissection studies determined that lung macrophage-enriched populations were the source of MCP-1 but not IL-8. Immunoreactivity to caspase 3 occurred within bronchioles and alveoli of day 6-infected lambs. In lung-draining lymph nodes, RSV induced lymphoid hyperplasia, suggesting an ability of RSV to enhance lymphocytic proliferation and differentiation pathways. This study suggests that, in lambs with moderate clinical disease, RSV enhances the activation of caspase cell death and Th1-skewed inflammatory pathways, and complements previous observations that emphasize the role of inflammation in the pathogenesis of RSV disease.
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Enfermedades del Recién Nacido/virología , Infecciones por Virus Sincitial Respiratorio/patología , Virus Sincitiales Respiratorios/inmunología , Animales , Animales Recién Nacidos , Niño , Humanos , Recién Nacido , Enfermedades del Recién Nacido/inmunología , Inflamación/etiología , Inflamación/genética , Inflamación/virología , Interleucina-8/metabolismo , Pulmón/inmunología , Pulmón/patología , Macrófagos/patología , Macrófagos/fisiología , Receptores CCR2/metabolismo , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/aislamiento & purificación , Ovinos , Transcripción Genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Hepcidin is an antimicrobial peptide involved in regulating iron homeostasis. It is induced by iron overload and decreased by hypoxia and anemia. Hepcidin regulates iron metabolism by inhibiting iron absorption by the duodenum and by inhibiting macrophage iron recycling. Hepcidin is induced in hepatocytes during the acute-phase response by IL-6. Previously, we have shown that hepcidin is not induced in macrophages by IL-6 but is induced by the synergistic interaction of IFN-gamma and Mycobacterium tuberculosis infection. In the present study, we examined the pathways involved in inducing macrophage hepcidin expression. We show that TLRs TLR2 and TLR4 and the transcription factor STAT1 are required for induction of hepcidin mRNA. Hepcidin promoter activity is also synergistically induced in RAW264.7 macrophages by IFN-gamma and M. tuberculosis. NF-kappaB and C/CEBP binding sites are required for promoter activity. Binding of NF-kappaB (p50/p65) to the NF-kappaB site and STAT1 and C/EBPbeta to the C/CEBP site was confirmed by EMSA. Knockdown of STAT1 and C/EBPbeta expression in RAW264.7 cells with siRNA plasmids inhibited hepcidin promoter activity induced by IFN-gamma and M. tuberculosis. Together, these studies demonstrate that macrophage hepcidin expression is induced by the activation of STAT1 and NF-kappaB and the induction of C/EBPbeta expression.
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Péptidos Catiónicos Antimicrobianos/genética , Proteína beta Potenciadora de Unión a CCAAT/fisiología , Interferón gamma/fisiología , Infecciones por Mycobacterium/fisiopatología , FN-kappa B/fisiología , Factor de Transcripción STAT1/fisiología , Transcripción Genética , Animales , Células de la Médula Ósea/citología , Cartilla de ADN , Regulación de la Expresión Génica , Hepcidinas , Interferón gamma/genética , Interferón gamma/farmacología , Macrófagos/citología , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Infecciones por Mycobacterium/genética , Infecciones por Mycobacterium/patología , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/aislamiento & purificación , Mapeo Restrictivo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Preterm and young neonates have an increased predisposition to respiratory distress syndrome (RDS) associated with an immature development of lung surfactant. Glucocorticoids (GCs) are the major immunomodulatory agents used to increase lung development and reduce the mortality and morbidity of preterm infants with RDS. However, their safety remains uncertain, and the precise mechanisms by which they improve lung function are unclear. In previous studies, we found that vascular endothelial growth factor (VEGF) enhances the innate immune response by respiratory epithelial cells, causes a monocytic infiltration into the lung, and reduces the severity of infection by respiratory syncytial virus (RSV), a respiratory pathogen known to affect preterm infants at a high prevalence. The purpose of this study is to measure the effects of VEGF administration on local immune responses in neonatal lambs, as the ovine lung is well suited for comparison to the human lung, due to similarities in alveolar development, immune responses, and RSV susceptibility. We hypothesized that VEGF induces the expression of genes necessary for host immune responses. We analyzed global gene expression profiles in the lungs of neonate lambs treated with VEGF by real-time qPCR. We report that VEGF induced the expression of chemokines (IL-8, RANTES, MCP-1), cytokines (IFN-gamma, IL-6, TNF-alpha, GMCSF), Toll-like receptor (TLR)-4, complement family members (C3, CFB, CFH) and collectins (SP-A, SP-D). These results suggest that VEGF can regulate local immune gene expression in vivo and should be further explored as a potential exogenous therapy for various lung diseases.
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Perfilación de la Expresión Génica , Pulmón/efectos de los fármacos , Pulmón/inmunología , Síndrome de Dificultad Respiratoria del Recién Nacido/inmunología , Factor A de Crecimiento Endotelial Vascular/farmacología , Animales , Animales Recién Nacidos , Quimiocinas/biosíntesis , Quimiocinas/genética , Colectinas/biosíntesis , Colectinas/metabolismo , Proteínas del Sistema Complemento/biosíntesis , Proteínas del Sistema Complemento/genética , Citocinas/biosíntesis , Citocinas/genética , Humanos , Recién Nacido , Pulmón/virología , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Infecciones por Virus Sincitial Respiratorio/inmunología , Ovinos , Receptores Toll-Like/biosíntesis , Receptores Toll-Like/genética , Factor A de Crecimiento Endotelial Vascular/uso terapéuticoRESUMEN
The ability to reliably analyze cellular and molecular profiles of normal or diseased tissues is frequently complicated by the inherent heterogeneous nature of tissues. Laser Capture Microdissection (LCM) is an innovative technique that allows the isolation and enrichment of pure subpopulations of cells from tissues under direct microscopic examination. Material obtained by LCM can be used for downstream assays including gene microarrays, western blotting, cDNA library generation and DNA genotyping. We describe a series of LCM protocols for cell collection, RNA extraction and qPCR gene expression analysis. Using reagents we helped develop commercially, we focus on two LCM approaches: laser cutting and laser capture. Reagent calculations have been pre-determined for 10 samples using the new PREXCEL-Q assay development and project management software. One can expect the entire procedure for laser cutting coupled to qPCR to take approximately 12.5-15 h, and laser capture coupled to qPCR to take approximately 13.5-17.5 h.
RESUMEN
Intracellular pathogens, including Mycobacterium tuberculosis, obtain iron from the host for their survival. Ferroportin 1 (FPN1; SLC40A1) is the sole iron exporter from mammalian cells and is expressed in the duodenum and macrophages. In the present study, we show that FPN1 mRNA levels in the mouse macrophage cell line RAW264.7 are synergistically induced by treatment with live or gamma-irradiated M. tuberculosis and IFN-gamma. FPN1 mRNA levels were also induced by Mycobacterium avium and IFN-gamma in RAW264.7 cells and the mouse alveolar macrophage cell line AMJ2-C8. Treatment of mouse resident peritoneal macrophages with M. tuberculosis and IFN-gamma resulted in a sixfold increase in FPN1 mRNA expression. In contrast, M. tuberculosis and IFN-gamma inhibited FPN1 mRNA expression in bone marrow-derived macrophages and lung macrophages, which have high basal levels of FPN1 mRNA expression. Using confocal microscopy, FPN1 protein localized rapidly to M. tuberculosis phagosomes after infection in RAW264.7 macrophages. In RAW264.7 cells expressing wild-type natural resistance-associated macrophage protein 1 (Nramp1(Gly169)), FPN1 and Nramp1 partially colocalized in late endosomes/lysosomes prior to infection. After 2 h of infection, Nramp1 and FPN1 were present in M. tuberculosis phagosomes. Our studies provide evidence for transcriptional regulation of FPN1 by pathogenic mycobacteria and IFN-gamma, which is dependent on the macrophage type. The trafficking of FPN1 to the M. tuberculosis phagosome suggests that it is involved in regulating iron availability to the mycobacteria in this locale.
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Proteínas de Transporte de Catión/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Peritoneales/metabolismo , Mycobacterium avium/fisiología , Mycobacterium tuberculosis/inmunología , Fagosomas/metabolismo , Tuberculosis/metabolismo , Animales , Western Blotting , Médula Ósea/inmunología , Médula Ósea/microbiología , Médula Ósea/patología , Proteínas de Transporte de Catión/genética , Células Cultivadas , Endosomas/inmunología , Endosomas/metabolismo , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Inmunidad Innata , Interferón gamma/farmacología , Hierro/metabolismo , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Lisosomas/inmunología , Lisosomas/metabolismo , Macrófagos Alveolares/microbiología , Macrófagos Peritoneales/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Mycobacterium tuberculosis/metabolismo , Fagosomas/inmunología , Fagosomas/microbiología , Tuberculosis/inmunología , Tuberculosis/patologíaRESUMEN
Hepcidin is an antimicrobial peptide produced by the liver in response to inflammatory stimuli and iron overload. Hepcidin regulates iron homeostasis by mediating the degradation of the iron export protein ferroportin 1, thereby inhibiting iron absorption from the small intestine and release of iron from macrophages. Here, we examined the expression of hepcidin in macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis. Stimulation of the mouse RAW264.7 macrophage cell line and mouse bone marrow-derived macrophages with mycobacteria and IFN-gamma synergistically induced high levels of hepcidin mRNA and protein. Similar results were obtained using the human THP-1 monocytic cell line. Stimulation of macrophages with the inflammatory cytokines IL-6 and IL-beta did not induce hepcidin mRNA expression. Iron loading inhibited hepcidin mRNA expression induced by IFN-gamma and M. avium, and iron chelation increased hepcidin mRNA expression. Intracellular protein levels and secretion of hepcidin were determined by a competitive chemiluminescence ELISA. Stimulation of RAW264.7 cells with IFN-gamma and M. tuberculosis induced intracellular expression and secretion of hepcidin. Furthermore, confocal microscopy analyses showed that hepcidin localized to the mycobacteria-containing phagosomes. As hepcidin has been shown to possess direct antimicrobial activity, we investigated its activity against M. tuberculosis. We found that hepcidin inhibited M. tuberculosis growth in vitro and caused structural damage to the mycobacteria. In summary, our data show for the first time that hepcidin localizes to the phagosome of infected, IFN-gamma-activated cells and has antimycobacterial activity.