RESUMEN
Sensory nerve endings within the wall of the gastrointestinal (GI) tract may respond to bacterial signalling, providing the basis for key biological processes that underlie intestinal motility and microbial homeostasis. Enteric neurons and smooth muscle cells are well known to express an array of receptors, including G-protein coupled receptors and ligand-gated ion channels, that can sense chemical ligands and other bacterially-derived substances. These include short chain fatty acids, secondary bile acids and lipopolysaccharide. For neural detection of microbial activators to occur, luminal substances must first interact with enterocytes for direct signalling or cross paracellularly. Recent studies indicate that bacterial-derived microvesicles can cross the gut epithelial barrier and affect motility. This suggests a possible intercellular communication pathway between the GI tract and the ENS. We explore the idea that bacterial microvesicles can behave as a delivery package for communication between microbe and host.
Asunto(s)
Colon/microbiología , Motilidad Gastrointestinal , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/fisiología , Células Receptoras Sensoriales/fisiología , Animales , Bacterias/metabolismo , Fenómenos Biológicos , Colon/inervación , Colon/fisiología , Tracto Gastrointestinal/inervación , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Células Receptoras Sensoriales/microbiología , Transducción de SeñalRESUMEN
The orchestration of host immune responses to enteric bacterial pathogens is a complex process involving the integration of numerous signals, including from the nervous system. Despite the recent progress in understanding the contribution of neuroimmune interactions in the regulation of inflammation, the mechanisms and effects of this communication during enteric bacterial infection are only beginning to be characterized. As part of this neuroimmune communication, neurons specialized to detect painful or otherwise noxious stimuli can respond to bacterial pathogens. Highlighting the complexity of these systems, the immunological consequences of sensory neuron activation can be either host adaptive or maladaptive, depending on the pathogen and organ system. These are but one of many types of neuroimmune circuits, with the vagus nerve and sympathetic innervation of numerous organs now known to modulate immune cell function and therefore dictate immunological outcomes during health and disease. Here, we review the evidence for neuroimmune communication in response to bacterial pathogens, and then discuss the consequences to host morbidity and mortality during infection of the gastrointestinal tract.
Asunto(s)
Sistema Nervioso Entérico/inmunología , Infecciones por Enterobacteriaceae/inmunología , Microbioma Gastrointestinal/inmunología , Tracto Gastrointestinal/inmunología , Neuroinmunomodulación/genética , Células Receptoras Sensoriales/inmunología , Animales , Péptido Relacionado con Gen de Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/inmunología , Citrobacter/crecimiento & desarrollo , Citrobacter/inmunología , Sistema Nervioso Entérico/microbiología , Infecciones por Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Tracto Gastrointestinal/inervación , Tracto Gastrointestinal/microbiología , Regulación de la Expresión Génica/inmunología , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Moléculas de Patrón Molecular Asociado a Patógenos/inmunología , Moléculas de Patrón Molecular Asociado a Patógenos/metabolismo , Células Receptoras Sensoriales/microbiología , Canal Catiónico TRPA1/genética , Canal Catiónico TRPA1/inmunología , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/inmunología , Receptores Toll-Like/genética , Receptores Toll-Like/inmunologíaRESUMEN
Host-associated microbiomes are emerging as important modifiers of brain activity and behavior. Metabolic, immune, and neuronal pathways are proposed to mediate communication across the so-called microbiota-gut-brain axis. However, strong mechanistic evidence, especially for direct signaling between microbes and sensory neurons, is lacking. Here, we discuss microbial regulation of short-chain fatty acids, neurotransmitters, as-yet-uncharacterized biochemicals, and derivatives of neuromodulatory drugs as important areas for assessing microbial interactions with the nervous system.
Asunto(s)
Encéfalo/microbiología , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Neurotransmisores/metabolismo , Células Receptoras Sensoriales/microbiología , Encéfalo/metabolismo , Tracto Gastrointestinal/metabolismo , Interacciones Huésped-Patógeno , Humanos , Células Receptoras Sensoriales/metabolismo , Transducción de SeñalRESUMEN
Pain and itch are unpleasant sensations accompanying many microbial infections. Recent studies demonstrate that pain- and itch-mediating somatosensory neurons are able to directly detect pathogens, triggering neuronal activation and subsequent regulation of immune responses. We discuss whether pain and/or itch during infection is beneficial or harmful to host antimicrobial defense.
Asunto(s)
Infecciones/fisiopatología , Dolor/microbiología , Prurito/microbiología , Inmunidad Adaptativa/inmunología , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata , Infecciones/inmunología , Infecciones/microbiología , Vías Nerviosas/inmunología , Vías Nerviosas/fisiología , Neuroinmunomodulación/inmunología , Dolor/inmunología , Prurito/inmunología , Células Receptoras Sensoriales/inmunología , Células Receptoras Sensoriales/microbiologíaAsunto(s)
Nociceptores/metabolismo , Dolor/microbiología , Células Receptoras Sensoriales/microbiología , Staphylococcus aureus/inmunología , Animales , Inmunidad Innata , Inflamación/microbiología , Ratones , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/metabolismo , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidadRESUMEN
This study investigated the distribution patterns of glial networks disclosed by reactivity for glial fibrillary acidic protein (GFAP) and S100B in healthy and carious human teeth. The objective was to determine the assembly and collapse of glial networks in response to encroaching infection. 15 healthy and 37 carious posterior teeth from adults were studied. Immediately after extraction, teeth were cleaned and vertically split and the half with pulp fixed and prepared for resin or frozen sections. Sections were stained with toluidine blue and for immunofluorescence, with observation by confocal laser microscopy and analysis by ImageJ software. Carious teeth were subdivided into three groups according to degree of carious involvement: microbial penetration through enamel (stage A), extension into dentin (stage B) and advanced penetration into dentin but without invasion of underlying pulp tissue (stage C). In stage A lesions there was marked increase in glial networks in dental pulp tissue that extended beyond the zone of microbial invasion. This response was maintained in stage B lesions. In advanced stage C lesions these networks were degraded in the zone of invasion in association with failure to contain infection. Cells expressing the glial markers GFAP and S100B showed a response to initial microbial invasion of dentin by increase in number and altered anatomical arrangement. The late stage of dentinal caries was marked by collapse of these networks in the region adjacent to advancing bacteria. This behaviour is important for understanding and explaining the defensive response of the neurosensory peripheral dental pulp apparatus to infection.
Asunto(s)
Coinfección/microbiología , Caries Dental/microbiología , Dentina/inervación , Neuroglía/patología , Adulto , Astrocitos/microbiología , Astrocitos/patología , Biomarcadores/análisis , Colágeno Tipo IV/análisis , Colorantes , Esmalte Dental/microbiología , Pulpa Dental/irrigación sanguínea , Pulpa Dental/inervación , Dentina/microbiología , Progresión de la Enfermedad , Secciones por Congelación , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Microvasos/microbiología , Microvasos/patología , Persona de Mediana Edad , Odontoblastos/microbiología , Odontoblastos/patología , Adhesión en Plástico , Subunidad beta de la Proteína de Unión al Calcio S100/análisis , Células Receptoras Sensoriales/microbiología , Cloruro de Tolonio , Vimentina/análisis , Adulto JovenRESUMEN
Acute Helicobacter pylori infection produces hypochlorhydria. The decrease in acid facilitates survival of the bacterium and its colonization of the stomach. The present study was designed to identify the pathways in oxyntic mucosa by which acute H. pylori infection inhibits acid secretion. In rat fundic sheets in an Ussing chamber, perfusion of the luminal surface with H. pylori in spent broth (10(3)-10(8) cfu/ml) or spent broth alone (1:10(5) to 1:10(0) final dilution) caused a concentration-dependent increase in somatostatin (SST; maximal: 200 ± 20 and 194 ± 9% above basal; P < 0.001) and decrease in histamine secretion (maximal: 45 ± 5 and 48 ± 2% below basal; P < 0.001); the latter was abolished by SST antibody, implying that changes in histamine secretion reflected changes in SST secretion. Both responses were abolished by the axonal blocker tetrodotoxin (TTX), the sensory neurotoxin capsaicin, or the CGRP antagonist CGRP8-37, implying that the reciprocal changes in SST and histamine secretion were due to release of CGRP from sensory neurons. In isolated rabbit oxyntic glands, H. pylori inhibited basal and histamine-stimulated acid secretion in a concentration-dependent manner; the responses were not affected by TTX or SST antibody, implying that H. pylori can directly inhibit parietal cell function. In conclusion, acute administration of H. pylori is capable of inhibiting acid secretion directly as well as indirectly by activating intramural CGRP sensory neurons coupled to stimulation of SST and inhibition of histamine secretion. Activation of neural pathways provides one explanation as to how initial patchy colonization of the superficial gastric mucosa by H. pylori can acutely inhibit acid secretion.
Asunto(s)
Aclorhidria/microbiología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Células Receptoras Sensoriales/metabolismo , Somatostatina/metabolismo , Aclorhidria/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Péptido Relacionado con Gen de Calcitonina/farmacología , Modelos Animales de Enfermedad , Ácido Gástrico/metabolismo , Fundus Gástrico/inervación , Fundus Gástrico/metabolismo , Fundus Gástrico/microbiología , Mucosa Gástrica/inervación , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Células HeLa , Infecciones por Helicobacter/microbiología , Histamina/metabolismo , Humanos , Células Parietales Gástricas/metabolismo , Células Parietales Gástricas/microbiología , Fragmentos de Péptidos/farmacología , Conejos , Ratas , Ratas Sprague-Dawley , Células Receptoras Sensoriales/efectos de los fármacos , Células Receptoras Sensoriales/microbiología , Bloqueadores de los Canales de Sodio/farmacología , Somatostatina/farmacología , Tetrodotoxina/farmacologíaRESUMEN
BACKGROUND: Burkholderia pseudomallei, the causative agent of melioidosis, is generally considered to be acquired via inhalation of dust or water droplets from the environment. In this study, we show that infection of the nasal mucosa is potentially an important portal of entry in melioidosis. METHODS: After intranasal inoculation of mice, infection was monitored by bioluminescence imaging and by immunohistological analysis of coronal sections. The bacterial loads in organ and tissue specimens were also monitored. RESULTS: Bioluminescence imaging showed colonization and replication in the nasal cavity, including the nasal-associated lymphoid tissue (NALT). Analysis of coronal sections and immunofluorescence microscopy further demonstrated the presence of infection in the respiratory epithelium and the olfactory epithelium (including associated nerve bundles), as well as in the NALT. Of significance, the olfactory epithelium and the brain were rapidly infected before bacteria were detected in blood, and a capsule-deficient mutant infected the brain without significantly infecting blood. CONCLUSIONS: These data suggest that the olfactory nerve is the route of entry into the brain and that this route of entry may be paralleled in cases of human neurologic melioidosis. This study focuses attention on the upper respiratory tract as a portal of entry, specifically focusing on NALT as a route for the development of systemic infection via the bloodstream and on the olfactory epithelium as a direct route to the brain.
Asunto(s)
Burkholderia pseudomallei , Tejido Linfoide/microbiología , Melioidosis/microbiología , Mucosa Olfatoria/microbiología , Animales , Burkholderia pseudomallei/citología , División Celular , Femenino , Proteínas Luminiscentes , Melioidosis/patología , Ratones , Ratones Endogámicos BALB C , Nariz/anatomía & histología , Nariz/microbiología , Bulbo Olfatorio/microbiología , Células Receptoras Sensoriales/microbiologíaRESUMEN
After intranasal instillation in the mouse, rabies virus (CVS strain) selectively infected olfactory receptor cells. In the main olfactory bulb (MOB), infection was observed in periglomerular, tufted, and mitral cells and in interneurons located in the internal plexiform layer. Beyond the MOB, CVS spread into the brain along the olfactory pathways. This infection is specific to chains of functionally related neurons but at the death of the animal some nuclei remain uninfected. CVS also penetrated the trigeminal system. The avirulent mutant AvO1, carrying a mutation in position 333 of the glycoprotein, infected the olfactory epithelium and the trigeminal nerve as efficiently as CVS. During the second cycle of infection, the mutant was able to infect efficiently periglomerular cells in the MOB and neurons of the horizontal limb of the diagonal band, which indicates that maturation of infective particles is not affected in primarily infected neuronal cells. On the other hand, other neuronal cells permissive for CVS, such as mitral cells or the anterior olfactory nucleus, are completely free of infection with the mutant, indicating that restriction is related to the ability of AvO1 to penetrate several categories of neurons. From these observations, we concluded that CVS should be able to bind several different receptors to penetrate neurons, while the mutant would be unable to recognize some of them.
Asunto(s)
Vías Olfatorias/microbiología , Virus de la Rabia/patogenicidad , Rabia/patología , Virulencia , Administración Intranasal , Animales , Encéfalo/microbiología , Línea Celular , Núcleo Celular/microbiología , Cricetinae , Epitelio/microbiología , Femenino , Ratones , Mutación , Virus de la Rabia/genética , Células Receptoras Sensoriales/microbiología , Nervio Trigémino/microbiología , Virulencia/genéticaRESUMEN
The skin samples of each palm side and dorsum side of finger, nose and peripheral nerves running under the finger skin at the area between proximal phalanx and distal phalanx of mangabey monkey A022 and rhesus monkey A125 were studied by histopathological methods (semithin section and light microscopic findings). Results found about this study were as follows. 1. In spite of the existence of a large amount of leprosy bacilli at the areas of corium and subcutis, some of Meissner's corpuscles, Vater-Pacinian corpuscles (or Golgi-Mazzoni's corpuscles) and Krauze's end bulbs-like structures were observed. 2. Occasionally, several intracytoplasmic foamy structures containing a large amount of leprosy bacilli were observed at the shallow and deep layers of stratum papillare of corium, where leprosy bacilli were not so remarkable as shown on Figure 4. So, it was thought that the affinity of leprosy bacilli to free nerve endings should be exist there. 3. Some of M. arrector pili were kept in good condition in spite of the existence of multiplying leprosy bacilli around the hair follicles. 4. It was thought that the histopathological findings of the fascicles of cutaneous nerves were classified to 4 patterns. The first pattern of histopathological finding of the cutaneous nerve was shown as A on Figure 25. In this pattern observed in almost of all the fascicles locating at the subcutis, no leprosy bacillus was observed inside the fascicles, and the nerve fibers were kept in good condition. The second pattern observed in almost of all the fascicles located at the corium, was shown as B on Figure 25. In this pattern, a large amount of leprosy bacilli were observed inside the fascicles, and the nerve fibers were often kept in good condition. The third pattern observed in almost of all the fascicles located at the deep layer of corium and subcutis, was shown as C on Figure 25. In this pattern, not only multiplying leprosy bacilli but also remarkable fibrosis were found inside one fascicle, and many nerve fibers disappeared by the existence of the bacilli and fibrosis. The final pattern observed in almost of all the fascicles located at the deep layer of corium and subcutis, was shown as D on Figure 25. In this pattern, remarkable fibrosis was observed inside the fascicles, and the nerve fibers often disappeared by the existence of fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Lepra/patología , Neuronas Aferentes/patología , Nervios Periféricos/patología , Células Receptoras Sensoriales/patología , Piel/inervación , Animales , Cebus , Dedos , Lepra/microbiología , Macaca mulatta , Mycobacterium leprae/crecimiento & desarrollo , Neuronas Aferentes/microbiología , Nariz , Células Receptoras Sensoriales/microbiologíaRESUMEN
Superficial epidermal surgical removal of a recurrent herpes simplex lesion within 36 hours of onset nearly always prevented recurrence in the site of excision. It is postulated that the surgery results in epidermal denervation, which prevents reinoculation of that epidermal site by the virus-laden sensory neuron. The procedure did not prevent further clinical expression of the disease at other epidermal sites innervated by the same or other infected neurons.
Asunto(s)
Herpes Simple/cirugía , Adulto , Balanitis/cirugía , Queilitis/cirugía , Desnervación/métodos , Epidermis/inervación , Epidermis/cirugía , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Dermatosis de la Mano/cirugía , Humanos , Masculino , Recurrencia , Células Receptoras Sensoriales/microbiología , Células Receptoras Sensoriales/cirugía , Simplexvirus/patogenicidad , Replicación ViralRESUMEN
Sensilla on the antenna of the bed bug, Cimex lectularius, were studied with the scanning and transmission electron microscope. Those which display a tubular body in the dendrite ending are presumed to have a mechanoreceptor function (bristles of type A, flat plate of type B). Bristles of type A1 contain additional dendrites which terminate at the tip of the bristle and may be gustatory receptors. Sensilla with pores in the hair wall are supposed to have an offactory, humidity and/or temperature receptor function (pegs and hairs of types C, D, E). Hairs of type E contain receptors for the alarm pheromones of the bed bug. Special attention has been paid to the pore structures and epicuticular layers of these sensilla. Possible differences in stimulus conduction are discussed between (i) sensilla with a simple wall and pores with pore tubules (types D and E) and (ii) the ribbed pegs (type C), which have a complex wall structure and spoke channels. The immersed cones of type F have a peculiar innervation, which has not been described previously. Two dendrites are held closely together by a third flat dendrite which wraps around them in the region of the outer segment. Coupling structures were found between the central dendrites, and between these and the third enveloping dendrite. Possible functions of this unique innervation are discussed. The dendrites innervating type D are grouped in three to eight bundles by multiple sheaths. The term thecogen cell is introduced to denote the innermost of the three sheath cells of a sensillum (the outer being the tormogen and the trichogen cell) which builds the dendrite sheath during ontogeny. Comparative morphometry revealed type-specific differences in the length and diameter of the dendrites. Some axons were found to lack any glial or perineurial sheath. Microorganisms were observed in the antennal tissue of several animals.