RESUMEN
We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD+ HD)] by the M strain and the laboratory strain H37Rv. Our results show that IL-1ß and IL-6 are crucial for the H37Rv and M-induced expansion of IL-17+ interferon (IFN)-γ- and IL-17+ IFN-γ+ in CD4+ T cells from MDR-TB and PPD+ HD. IL-23 plays an ambiguous role in T helper type 1 (Th1) and Th17 profiles: alone, IL-23 is responsible for M. tuberculosis-induced IL-17 and IFN-γ expression in CD4+ T cells from PPD+ HD whereas, together with transforming growth factor (TGF-ß), it promotes IL-17+ IFN-γ- expansion in MDR-TB. In fact, spontaneous and M. tuberculosis-induced TGF-ß secretion is increased in cells from MDR-TB, the M strain being the highest inducer. Interestingly, Toll-like receptor (TLR)-2 signalling mediates the expansion of IL-17+ IFN-γ- cells and the enhancement of latency-associated protein (LAP) expression in CD14+ and CD4+ T cells from MDR-TB, which suggests that the M strain promotes IL-17+ IFN-γ- T cells through a strong TLR-2-dependent TGF-ß production by antigen-presenting cells and CD4+ T cells. Finally, CD4+ T cells from MDR-TB patients infected with MDR Haarlem strains show higher IL-17+ IFN-γ- and lower IL-17+ IFN-γ+ levels than LAM-infected patients. The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response.
Asunto(s)
Memoria Inmunológica , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Mycobacterium tuberculosis/inmunología , Células Th17/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Tuberculosis Resistente a Múltiples Medicamentos/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Células Cultivadas , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Transducción de Señal , Especificidad de la Especie , Células Th17/microbiología , Receptor Toll-Like 2/metabolismo , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Pulmonar/microbiología , Adulto JovenRESUMEN
Sepsis and septic shock can be caused by Gram-positive and -negative bacteria and other microorganisms. In the case of Gram-negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, interferon (IFN)-γ and the concomitant induction of anti-inflammatory mediators such as IL-10, transforming growth factor (TGF)-ß or glucocorticoids, which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the main cause of the non-specific humoral and cellular immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that mifepristone (RU486), a known glucocorticoid receptor antagonist, could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, suggesting the involvement of endogenous glucocorticoids in this phenomenon. On the other hand, using cyclophosphamide and gemcitabine, we demonstrated that regulatory/suppressor CD4(+) CD25(+) forkhead boxP3(+) and GR-1(+) CD11b(+) cells do not play a major role in the establishment or the maintenance of endotoxin tolerance, a central mechanism for inducing an immunosuppression state.
Asunto(s)
Mifepristona/administración & dosificación , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Animales , Antígenos CD/biosíntesis , Ciclofosfamida/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Factores de Transcripción Forkhead/biosíntesis , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Lipopolisacáridos/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Mifepristona/farmacología , Receptores de Glucocorticoides/antagonistas & inhibidores , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/patología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , GemcitabinaRESUMEN
Tuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from gammadeltaT cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gammadeltaT from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gammadeltaT cells were differentiated by the CD3/gammadeltaT cell receptor (gammadeltaTCR) complex. The gammadeltaTCR(low) subset had a higher CD3 to TCR ratio and was enriched in Vdelta2(+) cells, whereas most Vdelta1(+) cells belonged to the gammadeltaTCR(high) subset. In PB from TB, most gammadeltaTCR(high) were CD45RA(+)CCR7(-) and gammadeltaTCR(low) were CD45RA(+/-)CCR7(+)CXCR3(+). In the pleural space the proportion of CD45RA(-)CCR7(+)CXCR3(+) cells was higher. Neither spontaneous nor Mtb-induced interferon (IFN)-gamma production was observed in PB-gammadeltaT cells from TB; however, PE-gammadeltaT cells showed a strong response. Both PB- and PE-gammadelta T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gammadeltaTCR(low) cells were the most potent effector cells. Thus, gammadeltaT cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gammadeltaT cells produce IFN-gamma within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile.
Asunto(s)
Complejo CD3/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Linfocitos T/inmunología , Tuberculosis Pleural/inmunología , Adolescente , Adulto , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Memoria Inmunológica , Interferón gamma/análisis , Proteína 1 de la Membrana Asociada a los Lisosomas/análisis , Proteínas de Membrana de los Lisosomas/análisis , Masculino , Persona de Mediana Edad , Perforina/análisisRESUMEN
The taxonomic status of Profilicollis ( = Falsifilicollis Webster, 1948) species in crustaceans in Chile is examined. Mole crabs, Emerita analoga (Stimpson 1857), living in the splash zone of a sandy beach at Lenga off the coast of central Chile, harbor Polymorphus (Profilicollis) bullocki Mateo, Córdova and Guzmán 1982, while the estuarine crabs, Hemigrapsus crenulatus (Milne-Edwards, 1837), living in an oligohaline inlet at the same site, harbor Profilicollis spp. cystacanths which cannot be distinguished specifically to either Profilicollis antarcticus or P. chasmagnathi Holcman-Spector, Mañé-Garzón and Dei-Cas 1977. We found no morphological data supporting records of P. altmani along the coast of Chile. Therefore, and after examination of both their morphology and the literature, we consider that P. bullocki must be reinstated as a valid species in the genus. There is a widespread distribution of habitats, such as sandy beaches and inlets, as well as a variety of host taxa involved in the life cycle of Profilicollis spp. Consequently, they provide an interesting scenario for testing hypotheses regarding the coevolution and host specificity of these parasites.
Asunto(s)
Acantocéfalos/clasificación , Anomuros/parasitología , Acantocéfalos/anatomía & histología , Acantocéfalos/aislamiento & purificación , Animales , ChileRESUMEN
Doasypsyllus (Neomipsyllus) aedon n. sp. is described from specimens obtained from Passeriform's nests (Troglodytidae and Furnariidae).
Asunto(s)
Enfermedades de las Aves/parasitología , Infestaciones Ectoparasitarias/veterinaria , Passeriformes/parasitología , Filogenia , Siphonaptera/clasificación , Animales , Enfermedades de las Aves/epidemiología , Chile/epidemiología , Infestaciones Ectoparasitarias/epidemiología , Infestaciones Ectoparasitarias/parasitología , Femenino , Masculino , Siphonaptera/anatomía & histologíaRESUMEN
The prevalence, abundance, and developmental status of the digenetic trematode Proctoeces lintoni Siddiqui et Cable 1960 were compared in 3 species of keyhole limpets Fissurella. A total of 197 limpets was collected at Caleta Chome, south-central Chile. Fissurella picta and F. costata had the highest prevalence of infection, whereas F. picta showed the greatest abundance of parasites, which increased with host shell length. However, the frequency of P. lintoni specimens with eggs in the uterus was greatest in F. costata. These results suggest that an increased rate of development of a parasite in the intermediate host may shorten the residence time necessary for maturation in the final host. Thus, faster development of the parasite in F. costata suggests the possibility that the parasites transmitted through this host species have shorter maturation times in clingfishes than individuals transmitted via other limpet species.