Lactococcus lactis subsp. Cremoris C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice

Abstract

Lactic acid bacteria (LAB), a major commensal bacterium in the small intestine, are well known beneficial bacteria which promote establishment of gut-centric immunity, such as anti-inflammation and anti-infection. In this report, we show that a LAB strain Lactococcus lactis subsp. Cremoris C60 possess an ability to activate antigen presenting cells, such as dendritic cells (DCs), and intestinal T cells which possibly support to maintain healthy intestinal immunological environment in aging process. We found that CD4+ T cells in the small intestine are dramatically decreased in aged Interleukin-18 knock out (IL-18KO) mice, associated with the impairment of IFN-γ production in the CD4+ T cells, especially in small intestinal lamina propria (LP). Surprisingly, heat killed-C60 (HK-C60) diet completely recovered the CD4+ T cells population and activity in SI-LP and over activated the population in Peyer’s patches (PPs) of IL-18KO mice. The HK-C60 diet was effective approach not only to restore the number of cells, but also to recover IFN-γ production in the CD4+ T cell population in the small intestine of IL-18-deficient mice. As a possible cause in the age-associated impairment of CD4+ T cells activity in IL-18KO mice, we found that the immunological activity was downregulated in the IL-18-deficient DCs. The cytokines production and cellular activation markers expression were downregulated in the IL-18-deficient bone marrow derived dendritic cells (BMDCs) at the basal level, however, both activities were highly upregulated in HK-C60 stimulation as compared to those of WT cells. Antigen uptake was also attenuated in the IL-18-deficient BMDCs, and it was significantly enhanced in the cells as compared to WT cells in HK-60 stimulation. An in vitro antigen presentation assay showed that IFN-γ production in the CD4+ T cells was significantly enhanced in the culture of IL-18-deficient BMDCs compared with WT cells in the presence of HK-C60. Thus, we conclude that HK-C60 diet possesses an ability to restore T cells impairment in the small intestine of IL-18-deficient environment. In addition, the positive effect is based on the immunological modification of DCs function which directory influences into the promotion of effector CD4+ T cells generation in the small intestine.

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

“…cremoris SK-11 and HP were both purchased from American Type Culture Collection (ATCC, Manassas, VA, USA). C60 was cultured by following the method described in a previous report [ 17 ]. The SK-11 and HP strains were cultured by following their product data sheets.…”

“…We previously reported that Lactococcus lactis subsp. cremoris C60, a probiotic LAB strain, promoted the generation and activation of CD4+ T cells in the small intestine [ 17 ]. As an underlying mechanism, we revealed that a heat-killed C60 (HK-C60) diet promoted not only cytokine production but also antigen-presenting activity for CD4+ T cells in intestinal DCs.…”

“…We have identified an immunological function of C60: this strain induced a strong immuno-modification in DCs that consequently promoted the activation of effector T cells [ 17 ]. While, previous studies have reported that various LAB strains have the potential to enhance the functions of macrophages, and this prompted us to investigate the novel immunological functions of C60 in macrophages [ 18 , 19 ].…”

RASAL3 Is a Putative RasGAP Modulating Inflammatory Response by Neutrophils

“…Bone marrow (BM) cells were obtained from the tibia and femur as previously reported ( 17 ). Briefly, the cells were flushed out from the tibia and femur using a 10 mL syringe with a 27 G needle containing cell culture medium.…”

Role of Gut Microbiota and Probiotics in Colorectal Cancer: Onset and Progression

“…A recent study of aged IL-18-deficient mice found that Lactococcus lactis subsp. cremoris C60 restored T cell populations in small intestinal lamina propria, which led to a rebound in IFN-γ production in the CD4 + T cell population [ 102 ]. Similarly, the probiotic strains Lactobacillus plantarum and Lactobacillus.…”