Infection-induced autoantibodies and pregnancy related pathology: an animal model

Abstract

In addition to being the main cause of mortality worldwide, bacterial and viral infections can be the cause of autoimmune and pregnancy disorders as well. The production of autoantibodies during infection can be explained by various mechanisms, including molecular mimicry, bystander cell activation and epitope spreading. Conversely, bacterial and viral infections during pregnancy are especially dangerous for the fetus. It is documented that infection-induced inflammatory processes mediated by Toll-like receptors (TLR) represent the main cause of preterm labour. We used two crucial bacterial components and TLR ligands, namely peptidoglycan and lipopolysaccharide, to stimulate BALB/c mice before immunisation with tetanus toxoid. Tetanus toxoid is an inactive form of the toxin produced by bacterium Clostridium tetani and shares structural similarity with plasma protein β2-glycoprotein I. Treatment with peptidoglycan and lipopolysaccharide in combination with tetanus toxoid induced the production of pathological autoantibodies, different fluctuations in natural autoantibodies and different types of reproductive pathology in treated animals, with peptidoglycan treatment being more deleterious. We propose that the production of pathological autoantibodies, TLR activation and changes in natural autoantibodies play crucial roles in infection-induced reproductive pathology in our animal model.