Glycosylation-dependent galectin-receptor interactions promote Chlamydia trachomatis infection

LUJAN AL; CROCI DO; GAMBARTE TUDELA J; LOSINO A; CAGNOLI A; MARIÑO KA; DAMIANI MT; RABINOVICH GA

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2018

0027-8424

Chlamydia trachomatis (Ct) constitutes the most prevalent sexually-transmitted bacterium worldwide for which no effective vaccine exists. Chlamydial infections can lead to severe sequelae including pelvic inflammatory disease, ectopic pregnancy and tubal infertility. As an obligate intracellular pathogen, Ct has evolved multiple strategies to promote adhesion and invasion of host cells, including those involving bacterial and host glycans. However, evidence about the involvement of host glycan-binding proteins in chlamydial infections is still lacking. Here, we show that galectin-1 (Gal1), an endogenous lectin abundantly expressed at sites of inflammation and microbial invasion, promoted Ct infection through N-glycan-dependent mechanisms. By the association to both, highly N-glycosylated bacterial membrane proteins and host cell receptors, Gal1 enhanced Ct attachment to cervical epithelial cells. Exposure to Gal1, mainly in its dimeric form, facilitated bacterial entry and increased the number of infected cells both in vitro and in vivo by favoring Ct-Ct and Ct-host cell interactions. These effects were confirmed in Gal1-deficient mice (Lgals1-/-) and mice lacking complex branched N-glycans (Mgat5-/-). Hence, this is the first report assigning a role for Gal1 in Ct infection outcome. Thus, targeting Gal1-N-glycan interactions may limit the severity of chlamydial infection by interfering bacterial invasion to host cells.