Data from: Evolution of the exclusively human-pathogen Neisseria gonorrhoeae: human-specific engagement of immunoregulatory Siglecs

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 adaptions 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.