Lactobacillus and Bifidobacterium Promote Antibacterial and Antiviral Immune Response in Human Macrophages

Abstract

Objective: The objective of this study was to identify the immunomodulatory potential of two consortia of lactic acid bacteria, “Lab4” and “Lab4b”, using human macrophages as an in vitro model system. Methods: THP-1 monocyte-derived macrophages were exposed to metabolites of Lab4 or Lab4b. RT-qPCR was performed on macrophages to determine the expression of M1 pro-inflammatory (IL-1β, IL-18 and CD80) or M2 anti-inflammatory (CD206) marker mRNA in addition to IL-1β protein and inflammasome (NLRP3, Caspase-1, NLRP1, NLRC4 and AIM2) mRNA expression. Bacterial (LPS and ATP) and viral (Poly I:C) challenge were stimulated to determine the potential of these consortia to regulate IL-1β protein, inflammasome mRNA expression, and antiviral IL-12 mRNA expression and protein under inflammatory conditions. The ability of these consortia to modulate macrophage phagocytosis of E. coliwas also assessed. Results:Results: Lab4 and Lab4b metabolites promoted an M1 phenotype in macrophages in vitro by increasing mRNA expression of IL-1β, IL-18, and CD80 and reducing mRNA expression of CD206. Induction of IL-1β protein suggested involvement of the inflammasome. mRNA expression of NLRP3, Caspase-1, NLRP1 and AIM2 was induced by Lab4 and mRNA expression of NLRP3 and Caspase-1 was induced by Lab4b suggesting different potential modes of action of the two consortia. Lab4 and Lab4b metabolites, in combination with this LPS and ATP challenge, enhanced IL-1β mRNA and protein expression further, accompanied by different mRNA expression profiles of inflammasome genes by the two consortia. Lab4 and Lab4b also induced expression of mRNA and protein of the antiviral response gene, IL-12. In combination with Poly I:C challenge, Lab4 induced IL-12 protein further, while Lab4b induced IL-12p25/IL-12p40 mRNA further highlighting potential differences. Both consortia were also able to induce phagocytosis of E. coli particles. Conclusion: Data generated from this study suggest the potential for organism-dependent control of the immunoregulatory response seen in human macrophages.