Characterization of the Human Inflammatory Response to Gardnerella vaginalis

Abstract

Gardnerella vaginalis is a Gram-positive bacterium associated with BV (BV), pelvic inflammatory disease, and preterm birth. BV is the most prevalent vaginal infection in women, characterized by the absence of normal Lactobacilli and overgrowth of G. vaginalis and other bacterial species. This study tested the hypothesis that G. vaginalis induces an inflammatory response in the human cell line, THP-1. The objectives of the study were to 1) determine whether different strains of G. vaginalis cause proinflammatory cytokinesproduction in THP-1 cells, 2) characterize intracellular pathways by which these cytokines are produced, and 3) determine molecular mechanisms involved in death of cells treated with strains of G. vaginalis.

In these studies, G. vaginalis strain 14018 induced statisticaliy significant increases in the inflammasome-dependent cytokines IL-1β, IL-18, as well as TNF-α in THP-1 monocytes. This same strain of G. vaginalis also caused statistically significant cell death in THP-1 monocytes and cleavage of caspase-1 by 24 h following treatment. Knockdown of the inflammasome component, NLRP3, in THP-1 cells reduced secretion of IL-1β. Additionally, THP-1 cells stably expressing ASC with a fluorescent tag exhibited colocalization of NLRP3 with ASC in G. vaginalis-treated THP-1 cells. These studies confirmed the role of the NLRP3 inflammasome in G. vaginalis inflammation.

In a strain-specific study, a statistically significant increase in THP-1 monocyte differentiation and IL-1β secretion were detected in response to G. vaginalis strains 14018 and 49145 but not strain 14019. Cytokine and inflammasome responses were similar for strains 14018 and 49145, but strain 14019 did not induce an inflammatory response in THP-1 cells.

The strain-specific ability of G. vaginalis to induce inflammation could contribute to the variability observed clinically between women colonized with G. vaginalis. The deleterious effects of G. vaginalis observed in THP-1 monocytes were not observed for the human trophoblast cell line HTR8 when treated with any of the G. vaginalis strains.

The results of these studies increase the understanding of how G. vaginalis activates the innate immune system and suggests that a strain-dependent activation of inflammation may be involved in BV and preterm birth.