Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization
Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization
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DOI：
10.1073/pnas.0500098102
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发表时间：
2005-02-22
影响因子：
11.1
通讯作者：
Klaenhammer, TR
中科院分区：
文献类型：
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作者：
Mohamadzadeh, M;Olson, S;Klaenhammer, TR
专业的抗原呈递树突状细胞（DCs）在全身和黏膜部位调节T细胞免疫反应中至关重要。许多乳酸杆菌属的菌种是人类肠道微生物群落的正常成员，并且大多数作为益生菌使用时被认为是安全的。由于树突状细胞在自然情况下或治疗过程中可能会接触到乳酸杆菌，我们研究了代表三种乳酸杆菌的几种明确菌株对人髓样树突状细胞（MDCs）的影响，发现它们调节了人髓样树突状细胞的表型和功能。接触乳酸杆菌的髓样树突状细胞上调了HLA - DR、CD83、CD40、CD80和CD86，并分泌高水平的白细胞介素 - 12（IL - 12）和白细胞介素 - 18（IL - 18），但不分泌白细胞介素 - 10（IL - 10）。在存在大肠杆菌脂多糖（LPS）的情况下，接触所有三种乳酸杆菌的髓样树突状细胞中白细胞介素 - 12持续存在，而脂多糖诱导的白细胞介素 - 10则受到极大抑制。用乳酸杆菌激活的髓样树突状细胞明显使CD4⁺和CD8⁺ T细胞向T辅助细胞1（T helper 1）和Tc1极化方向偏移，这可由干扰素 - γ（IFN - γ）的分泌证明，但白细胞介素 - 4（IL - 4）或白细胞介素 - 13（IL - 13）则未分泌。这些结果强调了乳酸杆菌在调节树突状细胞免疫功能方面可能具有的重要作用，并表明某些菌株作为疫苗佐剂可能特别有利，因为它们可促进树突状细胞将T细胞反应调节向T辅助细胞1和Tc1途径。
Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that they modulated the phenotype and functions of human MDCs. Lactobacillus-ex posed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10. IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited. MDCs activated with lactobacilli clearly skewed CD4(+) and CID8(+) T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN-gamma, but not IL-4 or IL-13. These results emphasize a potentially important role for lactobacilli in modulating immunological functions of DCs and suggest that certain strains could be particularly advantageous as vaccine adjuvants, by promoting DCs to regulate T cell responses toward T helper 1 and Tc1 pathways.