Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study

BACKGROUND: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. METHODS: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. RESULTS: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). CONCLUSIONS: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. FUNDING: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem

Evidence for Involvement of Th17 Type Responses in Post Kala Azar Dermal Leishmaniasis (PKDL)

Post kala azar dermal leishamniasis (PKDL), an unusual dermatosis, develops in 5–15% of apparently cured visceral leishmaniasis cases in India and in about 60% of cases in Sudan. PKDL cases assume importance since they constitute an important human reservoir for the parasite. Host immunological responses, considered as major factors in PKDL development, are poorly understood. Limited studies have been performed to explore the host immune responses and that too, restricted to a few immune parameters. The present study employed cDNA array technique that identified various host immuno-determinants including cytokines, chemokines, apoptotic and signaling molecules which were not reported previously in PKDL. In addition, we showed for the first time that Th17 responses are present during L. donovani infection in PKDL which possibly contributes significantly to disease pathogenesis by inducing TNF-α and nitric oxide production. Our findings lead to improved understanding of the host parasite interaction in terms of immune responses and pathology in tissue lesions of PKDL

Population dynamics during the Neolithic transition and the onset of megalithism in Portugal according to summed probability distribution of radiocarbon determinations

As field data accumulates, the study of Neolithic Portugal has been receiving increasing attention recently, from material culture and subsistence to ideology. However, little is known about population dynamics. In this paper, we use a judicious selection of radiocarbon determinations to evaluate demographic phenomena within the 9.500-5.000 cal BP range (thus, starting in the Late Mesolithic) making use of "summed probability distribution" analysis. In greater Portugal, results show a negative deviation (i.e. demographic decrease) at 6.400-6.300 cal BP and a positive deviation (i.e. demographic increase) at 5.350-4.950 cal BP. These can be explained, respectively, by the impact of farming about one millennium after its introduction (confirming the "Neolithic demographic transition" model) and by the full establishment of the "secondary products revolution" in the Late Neolithic. However, individual analyses of the northern and southern halves of the country-i.e. using the Mondego river valley as an ecological-geographical divide-show rather contrasting trajectories, with scarce Mesolithic populations and a demographic increase in the megalithism in the North, whereas in the South a demographic crisis occurred at the onset of megalithism (which remains to be fully explained) being followed in the Late Neolithic by a sharp demographic increase. Further summed probability distribution analyses of radiocarbon determinations, particularly if combined with other populational proxies, will be able in the future to detect other demographic events taking place in space and time.Juan de la Cierva postdoctoral grant [FJCI-2016-30588]Catalonian government [PGC2018-096943-B-C21]Spanish governmentSpanish GovernmentEuropean Commission [2017-SGR-1302]APOSTD Postdoctoral grant by the Valencian government [APOST/2019/179]info:eu-repo/semantics/publishedVersio

Effects of polyphenols and lipids from Pennisetum glaucum grains on T-cell activation: modulation of Ca2+ and ERK1/ERK2 signaling

International audienceBACKGROUND: Pearl millet (PM), i.e., Pennisetum glaucum, is widely grown in Africa and known for its anti-oxidant and anti-hyperlipidemic properties.METHODS: The P. glaucum grains were obtained from the region of Ouled Aïssa (South of Algeria). We assessed the effects of phenolic compounds and lipids, extracted from seeds of P. glaucum, on rat lymphocyte proliferation, activated by phorbol 12-myristate 13-acetate and ionomycin. In order to explore signaling pathway, triggered by these compounds, we assessed interleukin-2 (IL-2) mRNA expression and extracellular signal-regulated kinase-1/2 (ERK1/ERK2) phosphorylation. Finally, we determined increases in free intracellular Ca(2+) concentrations, [Ca(2+)]i, by employing Fura-2/AM in rat lymphocytes.RESULTS: The composition of P. glaucum grains in polyphenols was estimated to be 1660 µg gallic acid equivalents (GAE)/g. Lipids represented 4.5 %, and more than 72% of the fatty acids belonged to unsaturated family. Our investigation showed that both lipid and phenolic compounds inhibited mitogen-induced T-cell proliferation. Compared with phenolic compounds, lipids exerted weaker effects on ERK-1/ERK2 phosphorylation and Ca(2+) signaling in mitogen-activated T-cells.CONCLUSION: We conclude that the immunomodulatory effects of P. glaucum could be contributed by its phenolic and lipid contents