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© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Evolution of the exclusively human pathogen Neisseria gonorrhoeae: Human-specific engagement of immunoregulatory Siglecs
Author
Landig, Corinna S 1 ; Ashley, Hazel 2 ; Kellman, Benjamin P 3 ; Fong, Jerry J 1 ; Schwarz, Flavio 1 ; Agarwal, Sarika 4 ; Varki, Nissi 5 ; Massari, Paola 6 ; Lewis, Nathan E 7 ; Ram, Sanjay 4 ; Varki, Ajit 1   VIAFID ORCID Logo 

 Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California; Department of Medicine, University of California, San Diego, La Jolla, California 
 Department of Earth System Science, Stanford University, Stanford, California 
 Department of Pediatrics, University of California, San Diego, La Jolla, California; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, California 
 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 
 Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California; Department of Pathology, University of California, San Diego, La Jolla, California 
 Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts 
 Department of Pediatrics, University of California, San Diego, La Jolla, California; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, California; Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego, La Jolla, California 
Pages
337-349
Section
ORIGINAL ARTICLES
Publication year
2019
Publication date
Feb 2019
Publisher
John Wiley & Sons, Inc.
e-ISSN
17524571
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2170890374
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.