RESUMO
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Tuberculosis is the leading cause of death by an infectious disease worldwide1. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment. Tuberculosis increased accumulation of ILC subsets in the human lung, coinciding with a robust transcriptional response to infection, including a role in orchestrating the recruitment of immune subsets. Using mouse models, we show that group 3 ILCs (ILC3s) accumulated rapidly in Mtb-infected lungs and coincided with the accumulation of alveolar macrophages. Notably, mice that lacked ILC3s exhibited a reduction in the accumulation of early alveolar macrophages and decreased Mtb control. We show that the C-X-C motif chemokine receptor 5 (CXCR5)-C-X-C motif chemokine ligand 13 (CXCL13) axis is involved in Mtb control, as infection upregulates CXCR5 on circulating ILC3s and increases plasma levels of its ligand, CXCL13, in humans. Moreover, interleukin-23-dependent expansion of ILC3s in mice and production of interleukin-17 and interleukin-22 were found to be critical inducers of lung CXCL13, early innate immunity and the formation of protective lymphoid follicles within granulomas. Thus, we demonstrate an early protective role for ILC3s in immunity to Mtb infection.
Assuntos
Imunidade Inata/imunologia , Linfócitos/classificação , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Animais , Quimiocina CXCL13/imunologia , Feminino , Granuloma/imunologia , Granuloma/patologia , Humanos , Interleucina-17/imunologia , Interleucinas/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Linfócitos/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Receptores CXCR5/imunologia , Transcriptoma/genética , Tuberculose Pulmonar/genética , Interleucina 22RESUMO
INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.
Assuntos
Linfócitos B Reguladores/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Paraparesia Espástica Tropical/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Linfócitos B Reguladores/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Feminino , Humanos , Masculino , Paraparesia Espástica Tropical/virologia , Linfócitos T Reguladores/virologia , Carga ViralRESUMO
Abstract INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Linfócitos T CD4-Positivos/imunologia , Paraparesia Espástica Tropical/imunologia , Interferon gama/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos B Reguladores/imunologia , Linfócitos T CD4-Positivos/virologia , Paraparesia Espástica Tropical/virologia , Linfócitos T Reguladores/virologia , Linfócitos T CD8-Positivos/virologia , Carga Viral , Linfócitos B Reguladores/virologiaRESUMO
deficientes. Se describen prevalencias a nivel nacional de este mayores al 80%, con predominio de protozoos. Objetivo: describir la situación de parasitismo intestinal en preescolares de un hogar infantil estatal de Popayán (Colombia) y su relación con variables sociodemográficas. Materiales y métodos: se realizó un estudio descriptivo de corte transversal, entre mayo y septiembre de 2013, en 187 niños de 1 a 5 años de edad, matriculados en un hogar infantil estatal de Popayán (Colombia). Se realizó una encuesta sociodemográfica y análisis parasitológico de muestras de materia fecal mediante examen directo y método de concentración modificado de Ritchie-Frick. Se calcularon prevalencias, distribuciones de frecuencia y asociaciones de factores sociodemográficos con la presencia de parasitismo intestinal utilizando regresiones logísticas. Resultados: se identificó una prevalencia de parasitismo intestinal de 43,3%. La especie encontrada con mayor frecuencia fue Blastocystis spp. (24,6%), seguida por Entamoeba coli (13,4%) y Giardia intestinalis (11,8%). En ninguna de las muestras se observaron helmintos. Conclusiones: la prevalencia encontrada de parasitismo intestinal se aproxima al promedio nacional, de acuerdo con reportes para población preescolar en otros municipios del país. La ausencia de helmintos y el predominio de especies de protozoos respaldan la necesidad de futuras investigaciones que permitan conocer la epidemiología local. Además, se identificaron condiciones sociodemográficas de riesgo para infecciones en la población estudiada, algunas de ellas asociadas a la presencia de protozoos intestinales
Intestinal parasitism, generally asymptomatic problem but with important repercussions at socioeconomic and health field, mainly affects children with poor sanitary conditions. Their nationwide prevalence is higher than 80% with predominance of protozoa. Objective: To describe the situation of intestinal parasitism in preschools of a statechild's home in Popayan (Colombia) and its relationship with socio-demographic variables. Materials and methods: A cross - sectional descriptive study was carried out, between May and September 2013, with 187 children between 1 and 5 years of age, enrolled in a statechild's home in Popayan (Colombia). A sociodemographic survey was applied and parasitological analysis of stool samples was performed by direct examination and by the modified Ritchie-Frick concentration method. Prevalence and frequency distributions were calculated as well as logistic regression of associations of sociodemographic factors with the presence of intestinal parasitism. Results: The prevalence of intestinal parasites was 43.3%. The most frequently species was Blastocystis spp. (24.6%), followed by Entamoeba coli (13.4%) and Giardia instestinalis (11.8%). Helminths were not observed in any of the samples. Conclusions: The identified prevalence of intestinal parasites is close to the national average, according with previous reports for pre-school children in other municipalities in the country. The absence of helminths and the predominance of the protozoan species support the need for future research that allows knowing the local epidemiology. In addition, it was identified that the studied population is continuously exposed to different sociodemographic risk conditions that increase the possibility of acquiring enteroparasitosis