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

Suguru Saito,Nanae Kakizaki,Alato Okuno,Toshio Maekawa,Noriko M Tsuji

doi:10.3390/nu12113287

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.

Highlights

Lactic acid bacteria (LAB) are recognized as one of the beneficial bacterial strains in our body by contributing into the establishment of healthy intestinal immune environment [1]
Since IL-18 has been identified as an important cytokine in T cell activation and maintenance in various tissues and organs [29], we investigated whether IL-18 deficiency influences in T cell population of small intestine or not
As a major influenced population, we identified that CD3+ T cells were dramatically decreased in SI-lamina propria (LP) of aged IL-18 KO (Figure 1B)

Summary

Introduction

Lactic acid bacteria (LAB) are recognized as one of the beneficial bacterial strains in our body by contributing into the establishment of healthy intestinal immune environment [1]. Some LAB strains possess a unique effect in the enhancement and modification of immune responses in both innate and adaptive immunity [3,4]. LAB enhances innate immune cells activity, the subsequent immunological responses, such as Tcells activation in adaptive immunity, are driven to showing various immunological responses. This is a non-inflammatory response in the current understanding of immunology [5,6]

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Conclusion