RESUMEN
Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.
Asunto(s)
Evolución Molecular , Redes Reguladoras de Genes , Microglía/metabolismo , Enfermedades Neurodegenerativas/genética , Análisis de la Célula Individual , Transcriptoma , Animales , Pollos , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Primates , Reptiles , Roedores , Ovinos , Porcinos , Pez CebraRESUMEN
Humans are considered as the main host for Mycobacterium leprae1, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels2,3. Although naturally acquired leprosy has also been described in captive nonhuman primates4-7, the exact origins of infection remain unclear. Here we describe leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in Cantanhez National Park, Guinea-Bissau and Taï National Park, Côte d'Ivoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). These findings suggest that M. leprae may be circulating in more wild animals than suspected, either as a result of exposure to humans or other unknown environmental sources.
Asunto(s)
Lepra/veterinaria , Pan troglodytes/microbiología , Animales , Autopsia/veterinaria , Côte d'Ivoire , Heces/microbiología , Genotipo , Guinea Bissau , Humanos , Lepra/microbiología , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , FilogeniaRESUMEN
Nematodes belonging to the genus Oesophagostomum frequently infect wild chimpanzees (Pan troglodytes) across widely separated field sites. Nodular lesions (granulomas) containing Oesophagostomum are commonly seen in the abdomen of infected chimpanzees post-mortem. At Taï National Park, Côte d'Ivoire, previous studies have identified larvae of a variety of Oesophagostomum spp. in wild chimpanzee stool, based on sequencing of larval DNA, and nodular lesions associated with Oesophagostomum, identified morphologically to the genus level but not sequenced. Here we present three recent cases of parasitic granulomas found post-mortem in chimpanzees at Taï. We complement descriptions of gross pathology, histopathology and parasitology with PCR and sequencing of DNA isolated from the parasitic nodules and from adult worms found inside the nodules. In all three cases, we identify Oesophagostomum stephanostomum as the causative agent. The sequences from this study were identical to the only other published sequences from nodules in nonhuman primates-those from the wild chimpanzees of Gombe, Tanzania.
Asunto(s)
Enfermedades del Simio Antropoideo , Esofagostomiasis , Oesophagostomum , Pan troglodytes , Animales , Pan troglodytes/parasitología , Oesophagostomum/aislamiento & purificación , Oesophagostomum/genética , Côte d'Ivoire , Esofagostomiasis/veterinaria , Esofagostomiasis/parasitología , Enfermedades del Simio Antropoideo/parasitología , Granuloma/veterinaria , Granuloma/parasitología , Masculino , Femenino , Parques RecreativosRESUMEN
Lymphocytic choriomeningitis mammarenavirus (LCMV) is a globally distributed zoonotic pathogen transmitted by house mice (Mus musculus). We report the reemergence of LCMV (lineages I and II) in wild house mice (Mus musculus domesticus) and LCMV lineage I in a diseased golden lion tamarin (Leontopithecus rosalia) from a zoo in Germany.
Asunto(s)
Coriomeningitis Linfocítica , Enfermedades de los Roedores , Animales , Ratones , Virus de la Coriomeningitis Linfocítica , AlemaniaRESUMEN
Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.
Asunto(s)
Enfermedades de los Animales/mortalidad , Animales Salvajes/microbiología , Carbunco/veterinaria , Bacillus anthracis/patogenicidad , Mamíferos/microbiología , Bosque Lluvioso , Clima Tropical , África del Sur del Sahara , Enfermedades de los Animales/microbiología , Animales , Carbunco/microbiología , Carbunco/mortalidad , Bacillus anthracis/aislamiento & purificación , Dípteros/microbiología , Extinción Biológica , Femenino , Masculino , Pan troglodytes/microbiología , Parques Recreativos , FilogeniaRESUMEN
The platysma of the rhesus monkey consists of two parts: a platysma myoides located similar to the human platysma, and a platysma cervicale passing the dorsal cervical region and being in contact with the cheek pouch. Our investigation showed that the muscle fiber morphology was comparable in both parts. Muscle spindles were only present in regions connected to the cheek pouch and contained only nuclear chain fibers. It is tempting to speculate that they sense the filling of the cheek pouch rather than mimic activities.
Asunto(s)
Husos Musculares , Sistema Músculo-Aponeurótico Superficial , Animales , Mejilla , Macaca mulatta , Fibras Musculares Esqueléticas , Sistema Músculo-Aponeurótico Superficial/anatomía & histologíaRESUMEN
OBJECTIVE: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. DESIGN: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. RESULTS: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. CONCLUSION: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
RESUMEN
Yaws-like lesions are widely reported in wild African great apes, yet the causative agent has not been confirmed in affected animals. We describe yaws-like lesions in a wild chimpanzee in Guinea for which we demonstrate infection with Treponema pallidum subsp. pertenue. Assessing the conservation implications of this pathogen requires further research.
Asunto(s)
Buba , Animales , Guinea/epidemiología , Pan troglodytes , Treponema , Treponema pallidum/genética , Buba/epidemiología , Buba/veterinariaRESUMEN
Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons. The age dependence of seroprevalence is lost in nonhuman primates in captivity and in human migrants, raising the intriguing possibility that chronic life stress may be related to NMDAR1-AB formation, predominantly of the IgA class. Active immunization of ApoE-/- and ApoE+/+ mice against four peptides of the extracellular NMDAR1 domain or ovalbumin (control) leads to high circulating levels of specific AB. After 4 weeks, the endogenously formed NMDAR1-AB (IgG) induce psychosis-like symptoms upon MK-801 challenge in ApoE-/- mice, characterized by an open blood-brain barrier, but not in their ApoE+/+ littermates, which are indistinguishable from ovalbumin controls. Importantly, NMDAR1-AB do not induce any sign of inflammation in the brain. Immunohistochemical staining for microglial activation markers and T lymphocytes in the hippocampus yields comparable results in ApoE-/- and ApoE+/+ mice, irrespective of immunization against NMDAR1 or ovalbumin. These data suggest that NMDAR1-AB of the IgG class shape behavioral phenotypes upon access to the brain but do not cause brain inflammation on their own.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Trastornos Mentales/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Adulto , Animales , Autoanticuerpos/inmunología , Barrera Hematoencefálica , Encéfalo/inmunología , Gatos , Perros , Femenino , Humanos , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Masculino , Ratones , Proteínas del Tejido Nervioso/inmunología , Proteínas del Tejido Nervioso/metabolismo , Neuronas/inmunología , Primates , Ratas , Receptores de N-Metil-D-Aspartato/metabolismo , Estudios SeroepidemiológicosRESUMEN
We identified a novel Kaposi's sarcoma herpesvirus-related rhadinovirus (Colobine gammaherpesvirus 1) in a mantled guereza (Colobus guereza kikuyensis). The animal had multiple oral tumors characterized by proliferation of latent nuclear antigen 1-positive spindle cells and was not co-infected with immunosuppressive simian viruses, suggesting that it had Kaposi sarcoma caused by this novel rhadinovirus.
Asunto(s)
Enfermedades de los Monos/diagnóstico , Enfermedades de los Monos/virología , Rhadinovirus/clasificación , Rhadinovirus/genética , Sarcoma de Kaposi/veterinaria , Animales , Biopsia , Colobus , Femenino , Genes Virales , Genoma Viral , Inmunohistoquímica , Filogenia , Rhadinovirus/aislamiento & purificaciónRESUMEN
We determined the complete genome sequence of a virus isolated from a mantled guereza that died of primary effusion lymphoma. The virus is closely related to Kaposi's sarcoma-associated herpesvirus (KSHV) but lacks some genes implicated in KSHV pathogenesis. This finding may help determine how KSHV causes primary effusion lymphoma in humans.
Asunto(s)
Herpesvirus Humano 8/clasificación , Herpesvirus Humano 8/genética , Linfoma/veterinaria , Enfermedades de los Monos/diagnóstico , Enfermedades de los Monos/virología , Animales , Biopsia , Colobus , Genoma Viral , Genómica , Herpesvirus Humano 8/aislamiento & purificación , Inmunohistoquímica , Masculino , Enfermedades de los Monos/epidemiología , Filogenia , Secuenciación Completa del GenomaRESUMEN
Two nonrelated Goeldi's monkeys (Callimico goeldii) from the same enclosure developed multifocal alopecia with hyperkeratotic to ulcerative skin lesions on the lower abdomen and inner thighs. Necropsy samples of the first animal showed hyperplastic dermatitis together with in situ carcinoma and intralesional Demodex organisms. The second monkey developed similar lesions 2.5 yr later. Skin scrapings and biopsies also revealed Demodex mites within hyperplastic dermatitis. Long-term treatment with ivermectin, imidacloprid-moxidectin, and sarolaner resolved the demodicosis but skin lesions progressed to actinic keratosis and carcinoma. Both cutaneous neoplasia and demodicosis are rarely described in New World monkeys and these are the first reported cases in Goeldi's monkeys. Since the animals had access to ultraviolet (UV) light, as recommended for indoor-housed callitrichids, the skin tumors were likely UV-induced and the mites have settled particularly within impaired regions. Thus, apparent demodicosis can indicate cutaneous immunosuppression and might alert caretakers to adjust the UV regime.
Asunto(s)
Callimico , Carcinoma de Células Escamosas/veterinaria , Infestaciones por Ácaros/veterinaria , Enfermedades de los Monos/etiología , Neoplasias Cutáneas/veterinaria , Rayos Ultravioleta/efectos adversos , Animales , Animales de Zoológico , Antibacterianos/uso terapéutico , Antiparasitarios/administración & dosificación , Antiparasitarios/uso terapéutico , Azetidinas/administración & dosificación , Azetidinas/uso terapéutico , Carcinoma de Células Escamosas/patología , Combinación de Medicamentos , Femenino , Fluoroquinolonas/uso terapéutico , Insecticidas/administración & dosificación , Insecticidas/uso terapéutico , Ivermectina/uso terapéutico , Macrólidos/administración & dosificación , Macrólidos/uso terapéutico , Masculino , Infestaciones por Ácaros/tratamiento farmacológico , Infestaciones por Ácaros/parasitología , Enfermedades de los Monos/parasitología , Enfermedades de los Monos/patología , Neonicotinoides/administración & dosificación , Neonicotinoides/uso terapéutico , Nitrocompuestos/administración & dosificación , Nitrocompuestos/uso terapéutico , Neoplasias Cutáneas/etiología , Compuestos de Espiro/administración & dosificación , Compuestos de Espiro/uso terapéuticoRESUMEN
SFVmmu-DPZ9524 represents the third completely sequenced rhesus macaque simian foamy virus (SFV) isolate, alongside SFVmmu_K3T with a similar SFV-1-type env, and R289HybAGM with a SFV-2-like env. Sequence analysis demonstrates that, in gag and pol, SFVmmu-DPZ9524 is more closely related to R289HybAGM than to SFVmmu_K3T, which, outside of env, is more similar to a Japanese macaque isolate than to the other two rhesus macaque isolates SFVmmu-DPZ9524 and R289HybAGM. Further, we identify bel as another recombinant locus in R289HybAGM, confirming that recombination contributes to sequence diversity in SFV.
Asunto(s)
ADN Viral/genética , Macaca mulatta/virología , Enfermedades de los Monos/virología , Recombinación Genética , Infecciones por Retroviridae/veterinaria , Virus Espumoso de los Simios/genética , Animales , Expresión Génica , Productos del Gen env/genética , Productos del Gen gag/genética , Productos del Gen pol/genética , Filogenia , Infecciones por Retroviridae/virología , Análisis de Secuencia de ADN , Serogrupo , Virus Espumoso de los Simios/clasificación , Virus Espumoso de los Simios/aislamiento & purificaciónRESUMEN
A captive-born adult female Nilgiri langur ( Semnopithecus johnii) developed an edematous swelling of the left thigh and a firm mass around the right ankle joint. The animal also suffered from lethargy and anorexia and was euthanized because of poor general condition. Necropsy revealed that the skeletal muscle of the left thigh had been replaced by a multilocular cystic mass containing numerous sand-grain-sized whitish structures. Small cysts were also present in the lung and the myocardium. The mass of the right ankle joint was histologically consistent with a myxosarcoma. In contrast, the cystic masses from the left thigh, the lung, and the myocardium represented metacestode tissue with evidence of numerous larval cestodes consistent with cysticerci. Cysticerci showed morphological characteristics of Cysticercus longicollis, the larval form of Taenia crassiceps, which was confirmed by genetic analysis. This is the first documented case of a Taenia crassiceps cysticercosis in an Old World monkey species.
Asunto(s)
Colobinae , Cisticercosis/veterinaria , Cysticercus/aislamiento & purificación , Enfermedades de los Monos/diagnóstico , Animales , Animales de Zoológico , Cisticercosis/diagnóstico , Cisticercosis/parasitología , Femenino , Alemania , Enfermedades de los Monos/parasitologíaRESUMEN
Hallmarks of SIV infection are early depletion of gut CD4 T cells and diminished intestinal integrity. Comprehensive studies on colon biopsies of SIV-infected macaques efficiently controlling infection revealed that in contrast to viremic and failing controllers, elite controllers show preserved CD4 T cells, and low viral load, apoptosis, and inflammation.
Asunto(s)
Colon/inmunología , Macaca mulatta , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Animales , Apoptosis , Recuento de Linfocito CD4 , Colon/anatomía & histología , Colon/virología , India , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/fisiologíaRESUMEN
BACKGROUND: Due to a sporadic occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in non-human primates (NHP), the susceptibility of different NHP to MAP should be investigated. METHODS: Fecal and tissue samples (ileum, ileocecal lymph node, bone marrow) of 20 animals (seven species) were analyzed by IS900-based PCRs and sequenced. Samples of MAP PCR positive NHP were further cultivated. RESULTS: MAP DNA was detectable in two animals; the ileum of a cottontop tamarin and the bone marrow of a common marmoset. Cultivation of MAP failed. Sequence analysis revealed 100% homology to the MAP-K10 sequence. Pathohistological examinations offered no direct correlation to a MAP infection. CONCLUSIONS: MAP was detected for the first time in a common marmoset. But as both NHP suffered from other diseases, an asymptomatic infection with MAP was assumed. The detection of MAP in the bone marrow might play a role in establishing latent paratuberculosis, as known from tuberculosis.
Asunto(s)
Callitrichinae , Colobus , Macaca , Enfermedades de los Monos/epidemiología , Mycobacterium avium subsp. paratuberculosis/aislamiento & purificación , Paratuberculosis/epidemiología , Animales , Animales de Zoológico , ADN Bacteriano/análisis , Heces/microbiología , Femenino , Alemania/epidemiología , Incidencia , Masculino , Enfermedades de los Monos/microbiología , Paratuberculosis/microbiología , Reacción en Cadena de la PolimerasaRESUMEN
We isolated a monkeypox virus from a wild-living monkey, a sooty mangabey, found dead in Taï National Park, Côte d'Ivoire, in March 2012. The whole-genome sequence obtained from this isolate and directly from clinical specimens showed its close relationship to monkeypox viruses from Western Africa.
Asunto(s)
Cercocebus atys/virología , Genoma Viral , Monkeypox virus/genética , Mpox/virología , Filogenia , Animales , Animales Recién Nacidos , Côte d'Ivoire , Resultado Fatal , Secuenciación de Nucleótidos de Alto Rendimiento , Monkeypox virus/clasificación , Monkeypox virus/aislamiento & purificación , FilogeografíaRESUMEN
Infection of macaques with live attenuated simian immunodeficiency virus (SIV) usually results in long-lasting efficient protection against infection with pathogenic immunodeficiency viruses. However, attenuation by deletion of regulatory genes such as nef is not complete, leading to a high viral load and fatal disease in some animals. To characterize immunological parameters and polymorphic host factors, we studied 17 rhesus macaques infected with attenuated SIVmac239ΔNU. Eight animals were able to control viral replication, whereas the remaining animals (non-controllers) displayed variable set-point viral loads. Peak viral load at 2 weeks post-infection (p.i.) correlated significantly with set-point viral load (P<0.0001). CD4(+) T-cell frequencies differed significantly soon after infection between controllers and non-controllers. Abnormal B-cell activation previously ascribed to Nef function could already be observed in non-controllers 8 weeks after infection despite the absence of Nef. Two non-controllers developed an AIDS-like disease within 102 weeks p.i. Virus from these animals transmitted to naïve animals replicated at low levels and the recipients did not develop immunodeficiency. This suggested that host factors determined differential viral load and subsequent disease course. Known Mhc class I alleles associated with disease progression in SIV WT infection only marginally influenced the viral load in Δnef-infected animals. Protection from SIVmac251 was associated with homozygosity for MHC class II in conjunction with a TLR7 polymorphism and showed a trend with initial viral replication. We speculated that host factors whose effects were usually masked by Nef were responsible for the different disease courses in individual animals upon infection with nef-deleted viruses.