Am J Reprod Immunol. 2020 Mar;83(3):e13216. doi: 10.1111/aji.13216. Epub 2020 Jan 2.
Association of modulation of pro-inflammatory responses by dectin-2 with preterm delivery: An experimental model.
National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Service type: Knockout mice
Pro-inflammatory responses of pathogen recognition receptors (PRR) are implicated in preterm delivery (PTD). Dectin-2 is one PRR recognizing unselective carbohydrate structures; its participation in PTD has never been studied before.
METHOD OF STUDY: In an experimental model, PTD was induced in female pregnant wild type (WT) mice and mice with homologous deficiency for dectin-2 by the intraperitoneal injection of bacterial lipopolysaccharide (LPS) on day 14 of pregnancy. Time to delivery and fetal mortality were recorded. Challenged mice were sacrificed for tissue collection and splenocyte isolation six hours later. Concentrations of tumor necrosis factor-alpha (TNFα) and interleukin (IL)-1α and IL-1β were measured.
RESULTS: Delivery was induced significantly earlier in WT than dectin-2-/- mice; however fetal mortality was higher among dectin-2-/- mice. Candida albicans challenge could not lead to these changes. Sacrifice experiments showed that LPS challenge led to significant increase of TNFα, IL-1α and IL-1β in maternal tissues of WT; this was further enhanced for TNFα and IL-1β in dectin-2-/- mice. Pre-treatment with the prostaglandin inhibitor diclofenac delayed time to delivery of WT mice, but not of dectin2-/- mice. TNFα stimulation of splenocytes of dectin2-/- mice was enhanced with the addition of anti-TLR4 and decreased in the presence of lipid A.
CONCLUSIONS: Dectin-2 increases the risk of LPS-induced PTD by enhancing the production of pro-inflammatory cytokines.