Uptake of Levilactobacillus brevis JCM 1059 by THP-1 Cells via Interaction between SlpB and CAP-1 Promotes Cytokine Production

Abstract

Several probiotic lactic acid bacteria (LAB) exert immunomodulatory effects on the host. However, the reasons for the different effects of LAB have not been fully elucidated. To understand the different immunomodulatory effects of LAB, we evaluated the levels of critical molecules in differentiated monocytic THP-1 and dendritic cells (DCs) following the uptake of various LAB strains. Lactobacillus helveticus JCM 1120, Lactobacillus acidophilus JCM 1132, Levilactobacillus brevis JCM 1059, and Lentilactobacillus kefiri JCM 5818 showed significantly higher uptake among the 12 LAB species tested. The uptake of microbeads by THP-1 DC increased when coupled with the surface layer proteins (Slps) from the tested strains. SlpB was mainly observed in the L. brevis JCM 1059 Slps extract. The expected cell surface receptor for SlpB on THP-1 DC was purified using SlpB-coupled affinity resin and identified as adenylyl cyclase-associated protein 1 (CAP-1). SlpB binding to THP-1 DC decreased after the addition of anti-CAP-1 and anti-DC-SIGN antibodies but not after the addition of anti-macrophage-inducible C-type lectin (Mincle) antibody. These results suggest that SlpB on L. brevis JCM 1059 plays preferentially binds to CAP-1 on THP-1 DC and plays a crucial role in bacterial uptake by THP-1 cells as well as in subsequent interleukin-12 (IL-12) production.