Departments of Oral Molecular Microbiology, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan.
Departments of Biomaterials and Bioengineering, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan.
Arch Oral Biol. 2018 Sep;93:115-125. doi: 10.1016/j.archoralbio.2018.06.004. Epub 2018 Jun 4.
The purpose of this study is to elucidate differences in the mechanism of the IL-1β release-inducing activity of Candida albicans toward dendritic cells and macrophages because IL-1β is one of the proinflammatory cytokines which is crucial in host defense against candidiasis.
Two C. albicans strains were used in this study. One strain is uridine-auxotrophic (CAI4) that needs uridine to grow and form hyphae, and another is a strain without any specific auxotrophy (pACT1-GFP), which forms hyphae naturally by culturing with serum components. Murine macrophage and dendritic cell lines were primed with LPS and then stimulated with C. albicans CAI4 or pACT1-GFP.
Both strains of C. albicans induced IL-1β release from dendritic cells, and C. albicans pACT1-GFP induced IL-1β release but CAI4 induced little amounts in macrophages. These differences were suggested to be due to the difference in the amount of extracellular ATP released in the cell culture supernatants induced by C. albicans CAI4 or pACT1-GFP. For induction of IL-1β release from both macrophages and dendritic cells by C. albicans, direct contacts of the microbes with cells were required. In addition, macrophages required morphological change of C. albicans from yeast to hyphae for induction of IL-1β release, whereas dendritic cells did not require it. Dead C. albicans could induce IL-1β release from dendritic cells, but could not from macrophages.
There are different mechanisms by which C. albicans induces IL-1β release from dendritic cells and macrophages.
本研究旨在阐明白念珠菌诱导树突状细胞和巨噬细胞释放白细胞介素 1β（IL-1β）活性的机制差异，因为 IL-1β 是宿主防御假丝酵母菌病的关键促炎细胞因子之一。
本研究使用了两种白念珠菌菌株。一种是尿嘧啶营养缺陷型（CAI4）菌株，它需要尿嘧啶才能生长并形成菌丝，另一种是没有任何特定营养缺陷的菌株（pACT1-GFP），它通过与血清成分培养自然形成菌丝。用 LPS 预先刺激小鼠巨噬细胞和树突状细胞系，然后用 CAI4 或 pACT1-GFP 刺激白念珠菌。
两种白念珠菌菌株均能诱导树突状细胞释放 IL-1β，而 pACT1-GFP 诱导 IL-1β 释放，但 CAI4 诱导巨噬细胞释放的量很少。这些差异可能是由于 CAI4 或 pACT1-GFP 诱导的细胞培养上清液中细胞外 ATP 释放量的差异所致。为了诱导巨噬细胞和树突状细胞释放 IL-1β，白念珠菌需要与细胞直接接触。此外，白念珠菌从酵母形态向菌丝形态的形态变化是诱导巨噬细胞释放 IL-1β所必需的，而树突状细胞则不需要。死白念珠菌可以诱导树突状细胞释放 IL-1β，但不能诱导巨噬细胞释放。
白念珠菌诱导树突状细胞和巨噬细胞释放 IL-1β的机制不同。
