Lactococcus lactis subsp. cremoris C60 induces macrophages activation that enhances CD4+ T cell-based adaptive immunity

• Published in: Bioscience of Microbiota, Food and Health Food and Health, 2022, Vol.41(3), pp.130-136
• Main Authors: SAITO, Suguru, OKUNO, Alato, KAKIZAKI, Nanae, MAEKAWA, Toshio, TSUJI, Noriko M.
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Antigen presentation; Antigens; CD4 antigen; CD4+ T cells; CD80 antigen; CD86 antigen; Cell activation; Cytokines; Diet; IFN-γ; IL-12/IL-23p40; IL-6; Immune system; Immunity; Immunology; Inflammation; lactic acid bacteria; Lactococcus lactis; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Macrophages; Major histocompatibility complex; Probiotics; Stimulation; TNF-α; Toll-like receptors
• ISSN: 2186-3342; 2186-6953; 2186-3342
• DOI: 10.12938/bmfh.2021-057

Lactococcus lactis subsp. cremoris C60 is a probiotic strain that induces diverse functional modifications in immune cells. In this report, as a novel effect of C60 on myeloid lineage cells, we show that C60 enhances the immunological function of macrophages that consequently promotes CD4+ T cell activity in an antigen-dependent manner. Heat-killed (HK) C60 induced the production of pro-inflammatory cytokines in thioglycolate-elicited peritoneal macrophages (TPMs) much stronger than Toll-like receptor (TLR) ligand stimulation. The HK-C60 treatment also augmented the expression of antigen-presenting and co-stimulatory molecules, such as major histocompatibility complex (MHC) class II, CD80, and CD86, as well as antigen uptake in TPMs. These HK-C60-mediated functional upregulations in TPMs resulted in the promotion of CD4+ T cell activation in an antigen-dependent manner. Interestingly, the TPMs that originated from the mice fed the HK-C60 diet showed pre-activated characteristics, which was confirmed by the upregulation of cytokine production and antigen presentation-related molecule expression under lipopolysaccharide (LPS) stimulation. Furthermore, the antigen-dependent CD4+ T cell activation was also enhanced by the TPMs. This implied that antigen presentation activity was enhanced in the TPMs that originated from the HK-C60 diet mice. Thus, C60 effectively upregulates the immunological function of macrophages that directly connects to CD4+ T cell-based adaptive immunity.