Inhibitory Receptors Are Expressed by Trypanosoma cruzi-Specific Effector T Cells and in Hearts of Subjects with Chronic Chagas Disease

We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-γ)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-γ-producing CD4+ T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-γ-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4+CTAL-4+ T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-γ production. Conversely, CTLA-4 blockade did not improved IFN-γ production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4+LIR-1+ among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3+ T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease

Atlantic Leatherback Migratory Paths and Temporary Residence Areas

BACKGROUND: Sea turtles are long-distance migrants with considerable behavioural plasticity in terms of migratory patterns, habitat use and foraging sites within and among populations. However, for the most widely migrating turtle, the leatherback turtle Dermochelys coriacea, studies combining data from individuals of different populations are uncommon. Such studies are however critical to better understand intra- and inter-population variability and take it into account in the implementation of conservation strategies of this critically endangered species. Here, we investigated the movements and diving behaviour of 16 Atlantic leatherback turtles from three different nesting sites and one foraging site during their post-breeding migration to assess the potential determinants of intra- and inter-population variability in migratory patterns. METHODOLOGY/PRINCIPAL FINDINGS: Using satellite-derived behavioural and oceanographic data, we show that turtles used Temporary Residence Areas (TRAs) distributed all around the Atlantic Ocean: 9 in the neritic domain and 13 in the oceanic domain. These TRAs did not share a common oceanographic determinant but on the contrary were associated with mesoscale surface oceanographic features of different types (i.e., altimetric features and/or surface chlorophyll a concentration). Conversely, turtles exhibited relatively similar horizontal and vertical behaviours when in TRAs (i.e., slow swimming velocity/sinuous path/shallow dives) suggesting foraging activity in these productive regions. Migratory paths and TRAs distribution showed interesting similarities with the trajectories of passive satellite-tracked drifters, suggesting that the general dispersion pattern of adults from the nesting sites may reflect the extent of passive dispersion initially experienced by hatchlings. CONCLUSIONS/SIGNIFICANCE: Intra- and inter-population behavioural variability may therefore be linked with initial hatchling drift scenarios and be highly influenced by environmental conditions. This high degree of behavioural plasticity in Atlantic leatherback turtles makes species-targeted conservation strategies challenging and stresses the need for a larger dataset (>100 individuals) for providing general recommendations in terms of conservation

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Mecanismo de producción de los quistes artrósicos : estudio morfológico sobre 19 cabezas femorales artrósicas

19 osteoarthritic femoral heads obtained during total hip replacement procedure were studies. Photography, x-ray with mamograph and optical microscopy were then carried out. The authors analysed osteoarthritic cysts at different stages of development. By successive cuts they were able to demonstrate the communication of the cyst itself with the joint cavity. The authors believe that the filtration of synovial fluid in the subchondral bone might stimulate the proliferation of conjuntival cells

CTLA-4 and CD57 expression in the heart of chronic Chagas disease patients with severe cardiomyopathy.

<p>CTLA-4 and CD57 expression was assessed by immunohistochemistry in explanted heart tissue sections from chronic Chagas disease recipients. Two representative staining where CTLA-4 expression (arrows) was detected. Original magnification, 400× (A and B inset magnification, 1000×). Giant cell myocarditis infiltrate showing a typical giant cell (arrowhead), severe diffuse infíltrate and CTLA-4 expression (arrows). Original magnification 400× (C). No CTLA4⁺ cells were observed in idiopathic dilated cardiomyopathy heart tissues. Original magnification, 400× (D). CD57 expression in heart tissues from a <i>T. cruzi</i>-infected subject (E) and in lymph node tissues (F). Original magnification, 400×.</p

CD4⁺ T cells expressing LIR-1 following treatment with benznidazole in subjects with borderline or CD4⁺CTLA-4⁺ T cells under the cut-off value at baseline (A) and in untreated subjects after enrollment (B).

<p>PBMCs from <i>T. cruzi</i>-infected subjects were taken prior and at different time points following treatment with benznidazole or enrollment (in untreated subjects) and stained with anti-CD4 and anti-LIR-1 monoclonal antibodies. Plots show representative data for single subjects from a selected group. Significant changes in the levels of CD4⁺LIR-1⁺ T cells, as defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035966#s2" target="_blank">Materials and Methods</a> are depicted with dotted lines. <i>Horizontal line</i>, cut-off CD4⁺LIR-1⁺ T cell levels in the normal range, as defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035966#s2" target="_blank">Material and Methods</a>.</p

Increased frequencies of CD4⁺CTLA-4⁺ T cells following polyclonal activation with anti-CD3 antibodies.

<p>PBMCs were stimulated with anti-CD3 for 18 h or media alone. Cells were surface stained with anti-CD4 monoclonal antibody followed by fixation and permeabilization and intracellular staining with anti-CTLA-4 monoclonal antibody. Lymphocytes were gated by forward and side light scatter. From this population single color CD4 staining histogram was made and CD4⁺ T cells were selected and analyzed for CD4 vs. CTLA-4 dot plot. (A) Representative dot plots from an uninfected control, an asymptomatic subject (G0) and a patient with severe cardiomyopathy (G3). The numbers in the quadrants represent percent cells in each out of total CD4⁺ T cells. (B) The frequency of induced CD4⁺CTLA-4⁺ was calculated by subtracting the percentage of CD4⁺CTLA-4⁺ T cells in unstimulated cultures from the percentage of CD4⁺CTLA-4⁺ T cells responding to anti-CD3 stimulation. Values from individual uninfected controls, G0 or G3 subjects are depicted as separate points and median values are indicated by the horizontal lines. Kruskal-Wallis test with pairwise comparison was used to compare differences between subject groups.</p

Effect of cross-linking of CTLA-4 and LIR-1 on T cell responses against <i>T. cruzi</i>-antigens.

<p>IFN-γ ELISPOT responses of PBMCs from <i>T. cruzi</i>-infected subjects stimulated with <i>T. cruzi</i> lysate or media alone were measured in the presence of a plate bound isotype control, anti-CTLA-4 or anti-LIR-1 antibodies. The data represent the mean spot number/10⁶ PBMCs for individual subjects with positive IFN-γ ELISPOT responses prior to cross-linking assays. (*) Indicates significant differences in <i>T. cruzi</i>-specific IFN-γ ELISPOT responses (SFCs in media subtracted) between previous and post cross-linking assays, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035966#s2" target="_blank">Material and Methods</a>. The data represent the mean SFCs number/1×10⁶ PBMCs. ^(a) LIR-1 cross-linking was not performed. The clinical status of each subject is indicated between brackets.</p