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dc.contributor.authorLandig, Corinna S.
dc.contributor.authorHazel, Ashley
dc.contributor.authorKellman, Benjamin P.
dc.contributor.authorFong, Jerry J.
dc.contributor.authorSchwarz, Flavio
dc.contributor.authorAgarwal, Sarika
dc.contributor.authorVarki, Nissi
dc.contributor.authorMassari, Paola
dc.contributor.authorLewis, Nathan E.
dc.contributor.authorRam, Sanjay
dc.contributor.authorVarki, Ajit
dc.date2022-08-11T08:09:52.000
dc.date.accessioned2022-08-23T16:46:48Z
dc.date.available2022-08-23T16:46:48Z
dc.date.issued2019-01-03
dc.date.submitted2019-03-18
dc.identifier.citation<p>Evol Appl. 2019 Jan 3;12(2):337-349. doi: 10.1111/eva.12744. eCollection 2019 Feb. <a href="https://doi.org/10.1111/eva.12744">Link to article on publisher's site</a></p>
dc.identifier.issn1752-4571 (Linking)
dc.identifier.doi10.1111/eva.12744
dc.identifier.pmid30697344
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40951
dc.description.abstractNeisseria gonorrhoeae causes the sexually transmitted disease gonorrhea exclusively in humans and uses multiple strategies to infect, including acquisition of host sialic acids that cap and mask lipooligosaccharide termini, while restricting complement activation. We hypothesized that gonococci selectively target human anti-inflammatory sialic acid-recognizing Siglec receptors on innate immune cells to blunt host responses and that pro-inflammatory Siglecs and SIGLEC pseudogene polymorphisms represent host evolutionary adaptations to counteract this interaction. N. gonorrhoeae can indeed engage multiple human but not chimpanzee CD33rSiglecs expressed on innate immune cells and in the genitourinary tract--including Siglec-11 (inhibitory) and Siglec-16 (activating), which we detected for the first time on human cervical epithelium. Surprisingly, in addition to LOS sialic acid, we found that gonococcal porin (PorB) mediated binding to multiple Siglecs. PorB also bound preferentially to human Siglecs and not chimpanzee orthologs, modulating host immune reactions in a human-specific manner. Lastly, we studied the distribution of null SIGLEC polymorphisms in a Namibian cohort with a high prevalence of gonorrhea and found that uninfected women preferentially harbor functional SIGLEC16 alleles encoding an activating immune receptor. These results contribute to the understanding of the human specificity of N. gonorrhoeae and how it evolved to evade the human immune defense.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30697344&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectSiglecs
dc.subjectdisease biology
dc.subjectevolutionary medicine
dc.subjectgonorrhea
dc.subjectmicrobial biology
dc.subjectpolymorphism
dc.subjectpopulation genetics
dc.subjectsialic acid
dc.subjectBacteria
dc.subjectBacterial Infections and Mycoses
dc.subjectEcology and Evolutionary Biology
dc.subjectGenetics and Genomics
dc.subjectHemic and Immune Systems
dc.subjectImmunology and Infectious Disease
dc.subjectMicrobiology
dc.titleEvolution of the exclusively human pathogen Neisseria gonorrhoeae: Human-specific engagement of immunoregulatory Siglecs
dc.typeJournal Article
dc.source.journaltitleEvolutionary applications
dc.source.volume12
dc.source.issue2
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4764&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3750
dc.identifier.contextkey14048168
refterms.dateFOA2022-08-23T16:46:48Z
html.description.abstract<p>Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea exclusively in humans and uses multiple strategies to infect, including acquisition of host sialic acids that cap and mask lipooligosaccharide termini, while restricting complement activation. We hypothesized that gonococci selectively target human anti-inflammatory sialic acid-recognizing Siglec receptors on innate immune cells to blunt host responses and that pro-inflammatory Siglecs and SIGLEC pseudogene polymorphisms represent host evolutionary adaptations to counteract this interaction. N. gonorrhoeae can indeed engage multiple human but not chimpanzee CD33rSiglecs expressed on innate immune cells and in the genitourinary tract--including Siglec-11 (inhibitory) and Siglec-16 (activating), which we detected for the first time on human cervical epithelium. Surprisingly, in addition to LOS sialic acid, we found that gonococcal porin (PorB) mediated binding to multiple Siglecs. PorB also bound preferentially to human Siglecs and not chimpanzee orthologs, modulating host immune reactions in a human-specific manner. Lastly, we studied the distribution of null SIGLEC polymorphisms in a Namibian cohort with a high prevalence of gonorrhea and found that uninfected women preferentially harbor functional SIGLEC16 alleles encoding an activating immune receptor. These results contribute to the understanding of the human specificity of N. gonorrhoeae and how it evolved to evade the human immune defense.</p>
dc.identifier.submissionpathoapubs/3750
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages337-349


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© 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as © 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.