Differential dynamics of peripheral immune responses to acute SARS-CoV-2 infection in older adults

In this study, peripheral blood mononuclear cells from young and old patients with COVID-19 were examined phenotypically, transcriptionally and functionally to reveal age-, time- and severity-specific adaptations. Gene signatures within memory B cells and plasmablasts correlated with reduced frequency of antigen-specific B cells and neutralizing antibodies in older patients with severe COVID-19. Moreover, these patients exhibited exacerbated T cell lymphopenia, which correlated with lower plasma interleukin-2, and diminished antigen-specific T cell responses. Single-cell RNA sequencing revealed augmented signatures of activation, exhaustion, cytotoxicity and type I interferon signaling in memory T and natural killer cells with age. Although cytokine storm was evident in both age groups, older individuals exhibited elevated levels of myeloid cell recruiting factors. Furthermore, we observed redistribution of monocyte and dendritic cell subsets and emergence of a suppressive phenotype with severe disease, which was reversed only in young patients over time. This analysis provides new insights into the impact of aging on COVID-19

<i>Toll-like</i> receptors 2, 4, and 9 expressions over the entire clinical and immunopathological spectrum of American cutaneous leishmaniasis due to <i>Leishmania</i> <i>(V.) braziliensis</i> and <i>Leishmania (L.) amazonensis</i>

<div><p><i>Leishmania (V</i>.<i>) braziliensis</i> and <i>Leishmania(L</i>.<i>) amazonensis</i> are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCL^DTH+/++), borderline disseminated cutaneous leishmaniasis (BDCL^DTH±), anergic diffuse cutaneous leishmaniasis (ADCL^DTH-), and mucosal leishmaniasis (ML^DTH++++). It has recently been demonstrated, however, that while <i>L</i>. (<i>V</i>.) <i>braziliensis</i> shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), <i>L</i>. (<i>L</i>.) <i>amazonensis</i> drives the infection in the opposite direction to ADCL (the lowest T-cell hypersensitivity pole). This study evaluated by immunohistochemistry the expression of <i>Toll-like</i> receptors (<i>TLRs</i>) 2, 4, and 9 and their relationships with CD4 and CD8 T-cells, and TNF-α, IL-10, and TGF-β cytokines in that disease spectrum. Biopsies of skin and mucosal lesions from 43 patients were examined: 6 cases of ADCL, 5 of BDCL, and 11 of LCL caused by<i>L</i>. (<i>L</i>.) <i>amazonensis</i>; as well as 10 cases of LCL, 4 of BDCL, and 6 of ML caused by<i>L</i>. (<i>V</i>.) <i>braziliensis</i>. CD4⁺ T-cells demonstrated their highest expression in ML and, in contrast, their lowest in ADCL. CD8⁺ T-cells also showed their lowest expression in ADCL as compared to the other forms of the disease. TNF-α⁺showed increased expression from ADCL to ML, while IL-10⁺and TGF-β⁺ showed increased expression in the opposite direction, from ML to ADCL. With regards to <i>TLR</i>2, 4, and 9 expressions, strong interactions of <i>TLR</i>2 and 4 with clinical forms associated with <i>L</i>. (<i>V</i>.) <i>braziliensis</i> were observed, while <i>TLR</i>9, in contrast, showed a strong interaction with clinical forms linked to <i>L</i>. (<i>L</i>.) <i>amazonensis</i>. These findings strongly suggest the ability of <i>L</i>. (<i>V</i>.) <i>braziliensis</i> and <i>L</i>. (<i>L</i>.) <i>amazonensis</i> to interact with those <i>TLRs</i> to promote a dichotomous T-cell immune response in ACL.</p></div

Modulation of immune responses by targeting CD169/Siglec-1 with the glycan ligand

A fundamental role in the plant-bacterium interaction for Gram-negative phytopathogenic bacteria is played by membrane constituents, such as proteins, lipopoly- or lipooligosaccharides (LPS, LOS) and Capsule Polysaccharides (CPS). In the frame of the understanding the molecular basis of plant bacterium interaction, the Gram-negative bacterium Agrobacterium vitis was selected in this study. It is a phytopathogenic member of the Rhizobiaceae family and it induces the crown gall disease selectively on grapevines (Vitis vinifera). A. vitis wild type strain F2/5, and its mutant in the quorum sensing gene ΔaviR, were studied. The wild type produces biosurfactants; it is considered a model to study surface motility, and it causes necrosis on grapevine roots and HR (Hypersensitive Response) on tobacco. Conversely, the mutant does not show any surface motility and does not produce any surfactant material; additionally, it induces neither necrosis on grape, nor HR on tobacco. Therefore, the two strains were analyzed to shed some light on the QS regulation of LOS structure and the consequent variation, if any, on HR response. LOS from both strains were isolated and characterized: the two LOS structures maintained several common features and differed for few others. With regards to the common patterns, firstly: the Lipid A region was not phosphorylated at C4 of the non reducing glucosamine but glycosylated by an uronic acid (GalA) unit, secondly: a third Kdo and the rare Dha (3-deoxy-lyxo-2-heptulosaric acid) moiety was present. Importantly, the third Kdo and the Dha residues were substituted by rhamnose in a not stoichiometric fashion, giving four different oligosaccharide species. The proportions among these four species, is the key difference between the LOSs from both the two bacteria. LOS from both strains and Lipid A from wild type A. vitis are now examined for their HR potential in tobacco leaves and grapevine roots