Professor Tarvinder Dhanjal - Diamonds Funding Heart Rhythm Research

Dr Alexiane Decout - Lactobacillus Crispatus Surface Layer Proteins, Multifaceted Players of Women’s Health
Abstract: Preterm birth is the leading cause of death among children under the age of 5yrs. In 30% of cases, it is preceded by preterm prelabour rupture of the fetal membrane (PPROM). A risk indicator for PPROM is vaginal dysbiosis. Term pregnancy is associated with an optimal vaginal microbiota characterised by low diversity, with lactobacilli species constituting the vast majority of the bacteria therein. Conversely, a switch toward a more diverse microbiota containing opportunistic pathogenic species and a reduced proportion of lactobacilli is associated with increased risk of preterm birth. Inflammatory pathway activation associated with PPROM can be triggered by pro inflammatory stimuli such as TLR4 ligands. Yet, how the vaginal microbiota modulate the fetal immunological environment and thus PPROM risk is not fully understood.

Using clinical isolates of vaginal pathogens and commensals we identified that lactobacilli associated with term birth selectively interacted with anti-inflammatory innate immune receptors. A unique feature of lactobacilli surfaces is the presence of surface layer proteins (SLPs) forming a crystallin array. Removal of SLPs from the surface of L. crispatus restored a strong TLR2 activation, indicating that TLR2 ligands are present on L. crispatus, but are shielded by the S-layer proteins. These S-layer proteins interacted selectively with anti-inflammatory receptors such as DC-SIGN, were detected in the vaginal cervico-vaginal fluids and were associated with decreased maternal inflammation in L. crispatus dominated clinical samples. These data provide new insight into immunological mechanisms of microbial associated preterm birth and may offer new targets for novel preventive strategies.