Lactococcus lactis subsp. cremoris FC triggers IFN-γ production from NK and T cells via IL-12 and IL-18

Lactic acid bacteria (LAB) benefit health as probiotics in a strain-dependent way. In this study, we investigated the immunomodulatory effects of Lactococcus lactis subsp. cremoris FC (LcFC) on dendritic cells (DCs), natural killer (NK) cells and T cells. LcFC induced the production of cytokines such as IL-10, IL-12, IL-6 and TNF-α from murine bone marrow DCs (BMDCs) via MyD88-dependent pathway. In comparison with the type strain L. lactis subsp. cremoris ATCC 19257, LcFC induced particularly high production of IL-12 while induction of IL-6 was moderate. Consequently, LcFC triggered IFN-γ production in splenic NK, CD8+, and CD4+ cells. Most prominent effect of LcFC on IFN-γ production was observed in NK cells, followed by CD8+ cells, which was completely inhibited by combination of neutralizing anti-IL-12 and anti-IL-18 mAbs. Moreover, oral administration of LcFC enhanced the production of IFN-γ and IL-10 from splenocytes of treated mice. These findings suggest that this LAB strain is an efficient activator of protective cellular immunity via stimulation of myeloid cells including DCs.

► LcFC triggers IFN-γ production from NK, CD8+, and CD4+ cells. ► IFN-γ production induced by LcFC is mediated by accessory cells via IL-12 and IL-18. ► LcFC induces cytokine production from BMDC in MyD88-dependent manner. ► Oral administration of LcFC enhances IFN-γ production from splenocytes.