| First Author | Schwarz F | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 6 | Pages | 751-760 |
| PubMed ID | 28100677 | Mgi Jnum | J:264224 |
| Mgi Id | MGI:6195854 | Doi | 10.15252/embj.201695581 |
| Citation | Schwarz F, et al. (2017) Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen. EMBO J 36(6):751-760 |
| abstractText | Paired immune receptors display near-identical extracellular ligand-binding regions but have intracellular sequences with opposing signaling functions. While inhibitory receptors dampen cellular activation by recognizing self-associated molecules, the functions of activating counterparts are less clear. Here, we studied the inhibitory receptor Siglec-11 that shows uniquely human expression in brain microglia and engages endogenous polysialic acid to suppress inflammation. We demonstrated that the human-specific pathogen Escherichia coli K1 uses its polysialic acid capsule as a molecular mimic to engage Siglec-11 and escape killing. In contrast, engagement of the activating counterpart Siglec-16 increases elimination of bacteria. Since mice do not have paired Siglec receptors, we generated a model by replacing the inhibitory domain of mouse Siglec-E with the activating module of Siglec-16. Siglec-E16 enhanced proinflammatory cytokine expression and bacterial killing in macrophages and boosted protection against intravenous bacterial challenge. These data elucidate uniquely human interactions of a pathogen with Siglecs and support the long-standing hypothesis that activating counterparts of paired immune receptors evolved as a response to pathogen molecular mimicry of host ligands for inhibitory receptors. |
