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Tuberculosis (TB) alone caused over a billion deaths in the last 200 years, making it one of the deadliest diseases to humankind. Understanding the immune mechanisms underlying protection or pathology in TB is key to uncover the much needed innovative approaches to tackle TB. The scavenger receptor cysteine‐rich molecule CD5 antigen‐like (CD5L) has been associated with TB, but whether and how CD5L shapes the immune response during the course of disease remains poorly understood. Here, we show an upregulation of CD5L in circulation and at the site of infection in C57BL/6 Mycobacterium tuberculosis‐infected mice. To investigate the role of CD5L in TB, we studied the progression of M. tuberculosis aerosol infection in a recently described genetically engineered mouse model lacking CD5L. Despite the increase of CD5L during infection of wild‐type mice, absence of CD5L did not impact bacterial burden, histopathology or survival of infected mice. Absence of CD5L associated with a modest increase in the numbers of CD4+ T cells and the expression of IFN‐γ in the lungs of infected mice, with no major effect in overall immune cell dynamics. Collectively, this study confirms CD5L as a potential diagnostic biomarker to TB, showing no discernible impact on the outcome of the infection. [ABSTRACT FROM AUTHOR]

The focus of this work is on small municipalities (population below 50 thousand inhabitants) that cover around 87% of the territory of the Brazilian Legal Amazon (BLA). Based on a comprehensive integrated analysis approach using the three components hazard (climate extremes from CMIP6 future scenarios), exposure (directly affected population), and vulnerability (subdimensions of susceptibility and coping/adaptive capacity by using multidimensional indicators), the latter two using current datasets provided by the official Census IBGE 2022, we document a quantitative assessment of the risk R of natural disasters in the BLA region. We evidenced a worrying and imminent intensification of the curve of R in most Amazonian municipalities over the next two 25-year periods. The overall results of the highest proportions of R (total municipalities affected) pointed out the Amazonas, Roraima, Pará, and Maranhão as the main states, presenting projected categories of R high in the near future (2015 to 2039) and very high in the far future (2040 to 2064). The detailed assessment of the susceptibility and coping/adaptive capacity allowed us to elucidate the principal indicators that aggravate the degree of vulnerability: economy, the precariousness of urban infrastructure, medical services, communication, and urban mobility, whose combined factors, unfortunately, reveal a widespread poverty profile along the small Amazonian municipalities. Our scientific findings can assist decision makers in targeted strategies planning and public policies to minimize and mitigate ongoing and future climate change. [ABSTRACT FROM AUTHOR]

Summary: The characterization of the architecture, structure and extracellular interactions of the CD6 glycoprotein, a transmembrane receptor expressed in medullary thymocytes and all mature T‐cell populations, has been enhanced by the existence of monoclonal antibodies (mAbs) that specifically recognize the various scavenger receptor cysteine‐rich (SRCR) domains of the ectodomain. Using engineered isoforms of CD6 including or excluding each of the three SRCR domains, either expressed at the membranes of cells or in soluble forms, we provide conclusive and definitive evidence that domain 2 of CD6, previously not identifiable, can be recognized by the CD6 mAbs OX125 and OX126, and that OX124 targets domain 3 and can block the interaction at the cell surface of CD6 with its major ligand CD166. Alternative splicing‐dependent CD6 isoforms can now be confidently identified. We confirm that following T‐cell activation there is a partial replacement of full‐length CD6 by the CD6Δd3 isoform, which lacks the CD166‐binding domain, and we find no evidence for the expression of other CD6 isoforms at the mRNA or protein levels. [ABSTRACT FROM AUTHOR]

The scavenger receptor cysteine-rich (SRCR) family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP) of bacteria, fungi, or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion, which contains five SRCR modules, and a large C-terminal mucin-like domain. Toward establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR) properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSc5D (N-SSc5D), thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to Escherichia coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively), and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time, and label-free surface plasmon resonance (SPR)-based assay and examined the capacity of N-SSc5D, Spα, sCD5, and sCD6 to bind to different bacteria. We demonstrated that N-SSc5D compares with Spα in the capacity to bind to E. coli and Listeria monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3). Our work thus advocates the utility of SPR-based assays as sensitive tools for the rapid screening of interactions between immune-related receptors and PAMP-bearing microbes. The analysis of our results suggests that SRCR domains of different members of the family have a differential capacity to interact with bacteria, and further that the same receptor can discriminate between different bacteria strains and species. [ABSTRACT FROM AUTHOR]