The local skin cellular immune response determines the clinical outcome of sarcoptic mange in Iberian ibex (Capra pyrenaica)

[EN] Introduction: Sarcoptic mange, caused by Sarcoptes scabiei, is a disease with implications for wildlife conservation and management. Its severity depends on the host’s local skin immune response, which is largely unknown in Iberian ibex (Capra pyrenaica), a mountain ungulate dramatically affected by mange. In this species, the clinical outcome of sarcoptic mange varies among individuals, and the local immune response could be key to controlling the infestation. This study aims to characterize the local cellular immune response and its relationship with the clinical outcome. Methods: Fourteen Iberian ibexes were experimentally infested with S. scabiei and six more served as controls. Clinical signs were monitored, and skin biopsies were collected from the withers at 26, 46, and 103 days post-infection (dpi). The presence and distribution of macrophages (including M1 and M2 phenotypes), T lymphocytes, B lymphocytes, plasma cells, and interleukine 10 were quantitatively evaluated using immunohistochemical techniques. Results: An inflammatory infiltrate that decreased significantly from 26 to 103 dpi was observed in all the infested ibexes. The predominant inflammatory cell population in the skin of the mangy ibexes was formed by macrophages (mainly the M2 phenotype) followed by T lymphocytes, with lower numbers of B lymphocytes and plasma cells. Three clinical courses were identified: total recovery, partial recovery, and terminal stage. The inflammatory infiltrates were less pronounced in the fully recovered ibexes than in those that progressed to the terminal stage throughout the study. Discussion: The results suggest an exacerbated but effective Th1-type cellular immune response controlling mange in Iberian ibex. Furthermore, the local immune response appears to determine the variability of the clinical responses to S. scabiei infestation in this species. This first report on the progression of local skin immune cells is relevant not only for individuals but also for population management and conservation.SIThis project was funded by the Consejería de Medio Ambiente de la Junta de Andalucía (project 173/2009/M/00;03/15/M/00; 861_11_M_00 and 2016/00014/M) and the Spanish Ministerio de Economía y Competitividad (projects CGL2012-40043-C02-01, CGL2012-40043-C02-02, and CGL2016-80543-P). The authors’ research activities are partially supported by the Plan Andaluz de Investigación (RNM-118 group). MV is supported by a FI-GENCAT Fellowship (2020_FI_B2_00049, which is cofinanced by the Agència de Gestió d’Ajuts Universitaris i de Recerca and the European Social Fund). GM is a Serra Húnter FellowThe authors would like to thank the Consejería de Medio Ambiente de la Junta de Andalucía and in particular the Sierra Nevada Natural Space for their logistical support and the Sierra de Huétor Natural Park for the transfer of their experimental facilities. We also give special thanks to the park wardens and fieldworkers in the SNNS and above all to Apolo Sánchez, José López, Isidro Puga, Elías Martínez, Francisco Felipe, and Antonio Rodríguez for their professional and personal involvement in the study. The authors are also grateful to Manolo Herrera for the maintenance of the ibex and the facilities during the experimental phase, Emmanuel Serrano for advice, and the Service of Veterinary Pathology of the UAB for the histological preparation of samples. The technical and human support provided by Marta Silva is gratefully acknowledged

The local skin cellular immune response determines the clinical outcome of sarcoptic mange in Iberian ibex (Capra pyrenaica)

Sarcoptic mange, caused by Sarcoptes scabiei, is a disease with implications for wildlife conservation and management. Its severity depends on the host's local skin immune response, which is largely unknown in Iberian ibex (Capra pyrenaica), a mountain ungulate dramatically affected by mange. In this species, the clinical outcome of sarcoptic mange varies among individuals, and the local immune response could be key to controlling the infestation. This study aims to characterize the local cellular immune response and its relationship with the clinical outcome. Fourteen Iberian ibexes were experimentally infested with S. scabiei and six more served as controls. Clinical signs were monitored, and skin biopsies were collected from the withers at 26, 46, and 103 days post-infection (dpi). The presence and distribution of macrophages (including M1 and M2 phenotypes), T lymphocytes, B lymphocytes, plasma cells, and interleukine 10 were quantitatively evaluated using immunohistochemical techniques. An inflammatory infiltrate that decreased significantly from 26 to 103 dpi was observed in all the infested ibexes. The predominant inflammatory cell population in the skin of the mangy ibexes was formed by macrophages (mainly the M2 phenotype) followed by T lymphocytes, with lower numbers of B lymphocytes and plasma cells. Three clinical courses were identified: total recovery, partial recovery, and terminal stage. The inflammatory infiltrates were less pronounced in the fully recovered ibexes than in those that progressed to the terminal stage throughout the study. The results suggest an exacerbated but effective Th1-type cellular immune response controlling mange in Iberian ibex. Furthermore, the local immune response appears to determine the variability of the clinical responses to S. scabiei infestation in this species. This first report on the progression of local skin immune cells is relevant not only for individuals but also for population management and conservation

Histopathology, microbiology and the inflammatory process associated with Sarcoptes scabiei infection in the Iberian ibex, Capra pyrenaica

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.[EN]Background: Sarcoptic mange has been identified as the most significant infectious disease affecting the Iberian ibex (Capra pyrenaica). Despite several studies on the effects of mange on ibex, the pathological and clinical picture derived from sarcoptic mange infestation is still poorly understood. To further knowledge of sarcoptic mange pathology, samples from ibex were evaluated from histological, microbiological and serological perspectives. Methods: Samples of skin, non-dermal tissues and blood were collected from 54 ibex (25 experimentally infected, 15 naturally infected and 14 healthy). Skin biopsies were examined at different stages of the disease for quantitative cellular, structural and vascular changes. Sixteen different non-dermal tissues of each ibex were taken for histological study. Acetylcholinesterase and serum amyloid A protein levels were evaluated from blood samples from ibex with different lesional grade. Samples of mangy skin, suppurative lesions and internal organs were characterized microbiologically by culture. Bacterial colonies were identified by a desorption/ionization time-of-flight mass spectrometry system (MALDI TOF/TOF). Results: The histological study of the skin lesions revealed serious acanthosis, hyperkeratosis, rete ridges, spongiotic oedema, serocellular and eosinophilic crusts, exocytosis foci, apoptotic cells and sebaceous gland hyperplasia. The cellular response in the dermis was consistent with type I and type IV hypersensitivity responses. The most prominent histological findings in non-dermal tissues were lymphoid hyperplasia, leukocytosis, congestion and the presence of amyloid deposits. The increase in serum concentrations of acetylcholinesterase and amyloid A protein correlated positively with the establishment of the inflammatory response in mangy skin and the presence of systemic amyloidosis. A wide variety of bacterial agents were isolated and the simultaneous presence of these in mangy skin, lymph nodes and internal organs such as lungs, liver, spleen and kidney was compatible with a septicaemic pattern of infection. Conclusions: The alteration of biomarkers of inflammation and its implication in the pathogenesis of the disease and development of lesions in non-dermal tissues and septicaemic processes are serious conditioners for the survival of the mangy ibex. This severe clinical picture could be an important factor when considering the decision to eliminate animals that exceed a certain disease threshold from a population.SIThis study was funded by MINECO from the Spanish Government (grant numbers CGL2012-40043-C0-01, CGL2012-40043-CO2-02 and CGL2016-80543-P). The authors’ research activities are partially funded by the PAIDI Research Group RNM-118 from Junta de Andalucia. José Espinosa was supported by a PhD Grant (grant number ECC/1402/2013: BES-2013-063931). This study is part of the project "Bases biológicas para la gestión de la sarna sarcóptica en la cabra montés (Capra pyrenaica) de Sierra Nevada"

The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism