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Evolution of the exclusively human pathogen Neisseria gonorrhoeae: Humanâspecific engagement of immunoregulatory Siglecs
- Source :
- Evolutionary Applications, Evolutionary Applications, Vol 12, Iss 2, Pp 337-349 (2019), Evolutionary applications, vol 12, iss 2, Landig, Corinna S; Hazel, Ashley; Kellman, Benjamin P; Fong, Jerry J; Schwarz, Flavio; Agarwal, Sarika; et al.(2019). Evolution of the exclusively human pathogen Neisseria gonorrhoeae: Human-specific engagement of immunoregulatory Siglecs.. Evolutionary Applications, 12(2), 337-349. doi: 10.1111/eva.12744. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/3v03r2fh
- Publication Year :
- 2019
- Publisher :
- John Wiley and Sons Inc., 2019.
-
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.
- Subjects :
- Urologic Diseases
0106 biological sciences
0301 basic medicine
Sexually transmitted disease
Pseudogene
lcsh:Evolution
disease biology
Immune receptor
Biology
medicine.disease_cause
010603 evolutionary biology
01 natural sciences
polymorphism
Medicinal and Biomolecular Chemistry
03 medical and health sciences
chemistry.chemical_compound
Clinical Research
Genetics
medicine
lcsh:QH359-425
Ecology, Evolution, Behavior and Systematics
Evolutionary Biology
Innate immune system
gonorrhea
microbial biology
Inflammatory and immune system
SIGLEC
population genetics
Original Articles
respiratory system
Sialic acid
Complement system
Infectious Diseases
030104 developmental biology
chemistry
Siglecs
evolutionary medicine
sialic acid
Neisseria gonorrhoeae
HIV/AIDS
Sexually Transmitted Infections
Original Article
General Agricultural and Biological Sciences
Subjects
Details
- Language :
- English
- ISSN :
- 17524571
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Evolutionary Applications
- Accession number :
- edsair.doi.dedup.....f97c2db098ee576fa80054acd35b92eb