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Evol Appl. 2019 Jan 3;12(2):337-349. doi: 10.1111/eva.12744. eCollection 2019 Feb.

Evolution of the exclusively human pathogen Neisseria gonorrhoeae: Human-specific engagement of immunoregulatory Siglecs.

Author information

1
Glycobiology Research and Training Center University of California, San Diego La Jolla California.
2
Department of Cellular and Molecular Medicine University of California, San Diego La Jolla California.
3
Department of Medicine University of California, San Diego La Jolla California.
4
Department of Earth System Science Stanford University Stanford California.
5
Department of Pediatrics University of California, San Diego La Jolla California.
6
Bioinformatics and Systems Biology Graduate Program University of California, San Diego La Jolla California.
7
Department of Medicine University of Massachusetts Medical School Worcester Massachusetts.
8
Department of Pathology University of California, San Diego La Jolla California.
9
Department of Immunology Tufts University School of Medicine Boston Massachusetts.
10
Novo Nordisk Foundation Center for Biosustainability University of California, San Diego La Jolla California.

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.

KEYWORDS:

Siglecs; disease biology; evolutionary medicine; gonorrhea; microbial biology; polymorphism; population genetics; sialic acid

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