Editorial: Exploring Immune Variability in Susceptibility to Tuberculosis Infection in Humans.

Editorial on the Research Topic - Exploring Immune Variability in Susceptibility to Tuberculosis Infection in Humans. No abstract available

IgG glycosylation associates with risk of progression from latent to active tuberculosis

Glycosylation motifs shape antibody structure, stability and antigen affinity and play an important role in antibody localization and function. Serum IgG glycosylation profiles are significantly altered in infectious diseases, including tuberculosis (TB), but have not been studied in the context of progression from latent to active TB. We performed a longitudinal study of paired bulk IgG glycosylation and transcriptomic profiling in blood from individuals with active TB (ATB) or latent TB infection (LTBI) before and after treatment. We identified that a combination of two IgG1 glycosylation traits were sufficient to distinguish ATB from LTBI with high specificity and sensitivity, prior to, and after treatment. Importantly, these two features positively correlated with previously defined cellular and RNA signatures of ATB risk in LTBI, namely monocyte to lymphocyte ratio and the expression of interferon (IFN)-associated gene signature of progression (IFN-risk signature) in blood prior to treatment. Additional glycosylation features at higher prevalence in LTBI individuals with high expression of the IFN-risk signature prior to treatment included fucosylation on IgG1, IgG2 and IgG3. Together, our results demonstrate that bulk IgG glycosylation features could be useful in stratifying the risk of LTBI reactivation and progression to ATB

Plasmodium vivax but not Plasmodium falciparum blood-stage infection in humans is associated with the expansion of a CD8+ T cell population with cytotoxic potential

P. vivax and P. falciparum parasites display different tropism for host cells and induce very different clinical symptoms and pathology, suggesting that the immune responses required for protection may differ between these two species. However, no study has qualitatively compared the immune responses to P. falciparum or P. vivax in humans following primary exposure and infection. Here, we show that the two species differ in terms of the cellular immune responses elicited following primary infection. Specifically, P. vivax induced the expansion of a subset of CD8+ T cells expressing the activation marker CD38, whereas P. falciparum induced the expansion of CD38+ CD4+ T cells. The CD38+ CD8+ T cell population that expanded following P. vivax infection displayed greater cytotoxic potential compared to CD38- CD8+ T cells, and compared to CD38+ CD8+ T cells circulating during P. falciparum infection. We hypothesize that P. vivax infection leads to a stronger CD38+ CD8+ T cell activation because of its preferred tropism for MHC-I-expressing reticulocytes that, unlike mature red blood cells, can present antigen directly to CD8+ T cells. This study provides the first line of evidence to suggest an effector role for CD8+ T cells in P. vivax blood-stage immunity. It is also the first report of species-specific differences in the subset of T cells that are expanded following primary Plasmodium infection, suggesting that malaria vaccine development may require optimization according to the target parasite

Host Transcriptomics as a Tool to Identify Diagnostic and Mechanistic Immune Signatures of Tuberculosis

Tuberculosis (TB) is a major infectious disease worldwide, and is associated with several challenges for control and eradication. First, more accurate diagnostic tools that better represent the spectrum of infection states are required; in particular, identify the latent TB infected individuals with high risk of developing active TB. Second, we need to better understand, from a mechanistic point of view, why the immune system is unsuccessful in some cases for control and elimination of the pathogen. Host transcriptomics is a powerful approach to identify both diagnostic and mechanistic immune signatures of diseases. We have recently reported that optimal study design for these two purposes should be guided by different sets of criteria. Here, based on already published transcriptomics signatures of tuberculosis, we further develop these guidelines and identify additional factors to consider for obtaining diagnostic vs. mechanistic signatures in terms of cohorts, samples, data generation and analysis. Diagnostic studies should aim to identify small disease signatures with high discriminatory power across all affected populations, and against similar pathologies to TB. Specific focus should be made on improving the diagnosis of infected individuals at risk of developing active disease. Conversely, mechanistic studies should focus on tissues biopsies, immune relevant cell subsets, state of the art transcriptomic techniques and bioinformatics tools to understand the biological meaning of identified gene signatures that could facilitate therapeutic interventions. Finally, investigators should ensure their data are made publicly available along with complete annotations to facilitate metadata and cross-study analyses

Towards Harmonisation in Landscape Unit Delineation: An Analysis of Spanish Case Studies

[EN] The European Landscape Convention has encouraged member states to develop tools for landscape planning and management. Landscape character assessment is the most widespread approach. The aim of this paper is to identify the main trends in landscape unit delineation in Spain. For this purpose, 29 works are analysed by the Multiple Correspondence technique (MCA). Each work is characterised by a category of the variables: scale, type of extent, geomorphology, land matrix and visual boundaries. Results show that there is an implicit hierarchy in the way Spanish professionals are mapping landscape units. It is more apparent in variables related to geomorphology and less evident in variables related to land matrix. Regarding visual boundaries, they are not usually used at small scales and are more frequent at intermediate and large scales. The definition of clear criteria that allow comparable classifications and the increased consideration of cultural and perceptual factors is encouraged for future landscape character classifications.This work was supported by DGI and FEDER grant n8 AGL–2004-03263/AGR. We would like to thank Paz Aramburu, Rafael Escribano, Jordi Puig, the enterprise P&G and Florencio Zoido and Valencia Regional Department of Environment for the data provided for this research and also the R&D&I Linguistic Assistance Office at the Universidad Polite´cnica de Valencia for their help in revising and correcting this paper.Vallés-Planells, M.; Galiana, F.; Bru García, R. (2012). Towards Harmonisation in Landscape Unit Delineation: An Analysis of Spanish Case Studies. Landscape Research. 38(3):329-346. https://doi.org/10.1080/01426397.2011.647896S32934638

Systems approaches towards molecular profiling of human immunity

Systems immunology integrates cutting-edge technologies with bioinformatics to comprehensively interrogate the immune response to infection at an organismal level. Here, we review studies that have leveraged transcriptomic, genomic, proteomic, and metabolomic approaches towards the identification of cells, molecules, and pathways implicated in host–pathogen interactions. We discuss the potential of single cell technologies for the study of human immune responses and, in this context, we advocate that systems immunology provides a conceptual and methodological framework to harness these approaches to address longstanding questions of fundamental and applied immunology. Recognizing that the field is still in its infancy, we also discuss current limitations of systems immunology, as well as the need for validation of key findings for the discipline to fulfill its promise

Development of a cytokine-secreting-based assay for the identification, sorting and transcriptomic analysis of polyfunctional human T cells

Polyfunctional T cells that simultaneously produce the cytokines IFN-γ, IL-2 and TNF have been correlated with better clinical outcomes in various diseases. To date, cytokine polyfunctionality within T cells has been exclusively studied by intracellular cytokine staining coupled with flow cytometric analysis. Thus, further downstream interrogation of polyfunctional T cell characteristics such as transcriptomic analysis has not been possible. Here, we report the use of a flow cytometric method based on cytokine secretion assay technology to detect and isolate, for the first time, viable human polyfunctional T cells directly from in vitro stimulated whole blood samples. We demonstrate the successful application of this method to sort polyfunctional T cells obtained from human volunteers, which can be then used for downstream applications such as transcriptomic analysis using RTqPCR. This assay will facilitate in-depth investigations of T cells with distinct cytokine polyfunctionality, including defining their molecular profile and understanding the mechanisms regulating their generation and function

Innate interferons inhibit allergen and microbial specific T(H)2 responses

Several studies provided evidence of innate interferons (IFNs) regulating T(H)2 cytokine production using purified CD4(+) memory cells and T(H)2 polarisation via interleukin-4 (IL-4). Vitally, none of these previous studies examined IFN attenuation of T(H)2 responses to allergen or antigen. This study therefore sought to investigate the abrogation of specific allergen- and antigen-stimulated T(H)2 response in peripheral blood mononuclear cells (PBMC) derived from 12 sensitised individuals by IFN-beta and IFN-lambda. PBMC were cultured in the presence of house dust mite (HDM) allergen, rhinovirus (RV), influenza vaccine and tetanus toxoid (TT)+/- either IFN-beta or IFN-lambda for 3 and 5 days. IFN-gamma, IL-5 and IL-13 protein levels were measured by ELISA. Quantitative PCR (qPCR) was used to investigate induction of genes involved in control of T(H)2 cytokines. No alteration in T(H)1 IFN-gamma allergen/antigen response was observed with addition of IFN-beta or IFN-lambda. Consistent abrogation of T(H)2 response to HDM and influenza was observed with IFN-beta at both time points; attenuation was observed by day 5 with RV and TT. IFN-lambda had no consistent effect on T(H)2 production except in the presence of RV (multiplicity of infection 5); a decrease in IL-5 alone was observed in the presence of trivalent inactivated influenza vaccine. GATA binding protein 3 (GATA3) and suppressors of cytokine signalling3 mRNA were differentially regulated in HDM and influenza-stimulated cultures +/- IFN-beta. We concluded that IFN-beta produced a strong and consistent abrogation of T(H)2 cytokine production in the presence of a range of allergen and antigen stimulants. Immunology and Cell Biology (2012) 90, 974-977; doi: 10.1038/icb.2012.39; published online 24 July 201