@article {313256,
	title = {Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen.},
	journal = {EMBO J},
	volume = {36},
	number = {6},
	year = {2017},
	month = {Mar 15},
	pages = {751-760},
	abstract = {<p>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.</p>
},
	isbn = {0261-4189},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/28100677},
	author = {Schwarz, F and Landig, CS and Siddiqui, S and Secundino, I and Olson, J and Nissi M Varki and Nizet, V and Ajit Varki}
}
