<i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice
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 <i>Lactococcus lactis</i> subsp....
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MDPI AG
2020-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/11/3287 |
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| author | Suguru Saito Nanae Kakizaki Alato Okuno Toshio Maekawa Noriko M. Tsuji |
| author_facet | Suguru Saito Nanae Kakizaki Alato Okuno Toshio Maekawa Noriko M. Tsuji |
| author_sort | Suguru Saito |
| collection | DOAJ |
| description | 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 <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> 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. |
| first_indexed | 2024-03-10T15:18:46Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T15:18:46Z |
| publishDate | 2020-10-01 |
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| spelling | doaj.art-6d0c57f2a7d24cf185fce326d21abfa32023-11-20T18:42:04ZengMDPI AGNutrients2072-66432020-10-011211328710.3390/nu12113287<i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient MiceSuguru Saito0Nanae Kakizaki1Alato Okuno2Toshio Maekawa3Noriko M. Tsuji4Division of Cellular and Molecular Engineering, Department of Life Technology and Science, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 3058560, JapanDivision of Cellular and Molecular Engineering, Department of Life Technology and Science, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 3058560, JapanDivision of Cellular and Molecular Engineering, Department of Life Technology and Science, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 3058560, JapanDivision of Cellular and Molecular Engineering, Department of Life Technology and Science, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 3058560, JapanDivision of Cellular and Molecular Engineering, Department of Life Technology and Science, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 3058560, JapanLactic 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 <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> 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.https://www.mdpi.com/2072-6643/12/11/3287probioticssmall intestineintestinal immunityInterleukin-18IFN-γ+CD4+ T (Th1) cellsdendritic cells |
| spellingShingle | Suguru Saito Nanae Kakizaki Alato Okuno Toshio Maekawa Noriko M. Tsuji <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice Nutrients probiotics small intestine intestinal immunity Interleukin-18 IFN-γ+CD4+ T (Th1) cells dendritic cells |
| title | <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice |
| title_full | <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice |
| title_fullStr | <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice |
| title_full_unstemmed | <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice |
| title_short | <i>Lactococcus lactis</i> subsp. <i>Cremoris</i> C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice |
| title_sort | i lactococcus lactis i subsp i cremoris i c60 restores t cell population in small intestinal lamina propria in aged interleukin 18 deficient mice |
| topic | probiotics small intestine intestinal immunity Interleukin-18 IFN-γ+CD4+ T (Th1) cells dendritic cells |
| url | https://www.mdpi.com/2072-6643/12/11/3287 |
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