Information transfer in mammalian glycan-based communication

<p>Glycan-binding proteins, so-called lectins, are exposed on mammalian cell surfaces and decipher the information encoded within glycans translating it into biochemical signal transduction pathways in the cell. These glycan-lectin communication pathways are complex and difficult to analyze. However, quantitative data with single <span class="ins cts-3">-</span>cell resolution provide means to disentangle the associated signaling cascades. We chose C-type lectin receptors (<span class="jrnlPatterns">CTLs</span>) expressed on immune cells as a model system to study their capacity to transmit information encoded in glycans of incoming particles. In particular, we used <span class="del cts-4">NF-κB</span><span class="ins cts-4">nuclear factor kappa-B</span>-reporter cell lines expressing <span class="ins cts-4">DC-specific ICAM-3–grabbing nonintegrin<span class="ins cts-7"> <span class="ins cts-7">(DC-SIGN)</span></span></span><span class="del cts-4">DC-SIGN</span>, <span class="ins cts-4">macrophage C-type lectin (</span>MCL<span class="ins cts-4">)</span>, dectin-1, dectin-2, and <span class="del cts-4">mincle</span><span class="ins cts-4">macrophage-inducible C-type lectin<span class="ins cts-6"> (MINCLE)</span></span>, as well as TNFαR and TLR-1<span class="jrnlPatterns">&amp;</span><span class="jrnlPatterns">2</span> in monocytic cell lines and compared their transmission of glycan-encoded information. All receptors <span class="del cts-7">did </span>transmit information with similar signaling capacity, except dectin-2. This lectin was identified to <span class="ins cts-3">be </span>less efficient in information transmission compared to the other CTLs<span class="ins cts-3">,</span> and even wh<span class="del cts-7">ile </span><span class="ins cts-7">en </span>the sensitivity of the dectin-2 pathway was enhanced by overexpression of its co-receptor FcRγ, its transmitted information was not. Next, we expanded our investigation toward<span class="del cts-3">s</span> the integration of multiple signal transduction pathways including synergistic lectins, which is crucial during pathogen recognition. We show how the signaling capacity of lectin receptors using a similar signal transduction pathway (dectin-1 and dectin-2) <span class="del cts-3">are</span><span class="ins cts-3">is</span> being integrated by compromising between the lectins. In contrast, co-expression of MCL synergistically enhanced the dectin-2 signaling capacity, particularly at low <span class="ins cts-3">-</span>glycan stimulant concentration. By using dectin-2 and other lectins as examples, we demonstrate how signaling capacity of dectin-2 is modulated in the presence of other lectins<span class="ins cts-3">,</span> and therefore<span class="ins cts-3">,</span> the findings provide insight into how immune cells translate glycan information using</p>