Glycosylation-dependent galectin-receptor interactions promote <i>Chlamydia trachomatis</i> infection.

Abstract

<i>Chlamydia trachomatis</i> (<i>Ct</i>) constitutes the most prevalent sexually transmitted bacterium worldwide. Chlamydial infections can lead to severe clinical sequelae including pelvic inflammatory disease, ectopic pregnancy, and tubal infertility. As an obligate intracellular pathogen, <i>Ct</i> has evolved multiple strategies to promote adhesion and invasion of host cells, including those involving both bacterial and host glycans. Here, we show that galectin-1 (Gal1), an endogenous lectin widely expressed in female and male genital tracts, promotes <i>Ct</i> infection. Through glycosylation-dependent mechanisms involving recognition of bacterial glycoproteins and <i>N</i>-glycosylated host cell receptors, Gal1 enhanced <i>Ct</i> attachment to cervical epithelial cells. Exposure to Gal1, mainly in its dimeric form, facilitated bacterial entry and increased the number of infected cells by favoring <i>Ct</i>-<i>Ct</i> and <i>Ct</i>-host cell interactions. These effects were substantiated in vivo in mice lacking Gal1 or complex β1-6-branched <i>N</i>-glycans. Thus, disrupting Gal1-<i>N</i>-glycan interactions may limit the severity of chlamydial infection by inhibiting bacterial invasion of host cells.