細菌代謝物による腸内CX3CR1+細胞のGPR31依存型デンドライト突起
Naoki Morita1,2,3, Eiji Umemoto1,2,3, Setsuko Fujita4
1Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
Nature
|January 25, 2019
まとめ
細菌の代謝物質であるピルビック酸と乳酸は,GPR31経由で免疫細胞のデンドライト突起を誘発する. サルモネラ感染に対する免疫反応と耐性を高めます.
科学分野:
- 免疫学
- 微生物学
- 胃腸内科
背景:
- CX3CR1 (CX3CR1+細胞) を発現する小腸単核細胞は,免疫反応の調節に極めて重要です.
- これらの細胞は,デンドライトを腸の光に拡張することによって,ルミナル抗原を捕まえる.
- 腸内CX3CR1+細胞のデンドライト突起を誘発する正確なメカニズムはほとんど不明である.
研究 の 目的:
- 細菌代謝物が腸内CX3CR1+細胞のデンドライト突起を誘発するメカニズムを解明する.
- この過程におけるGタンパク質結合受容体31 (GPR31) の役割を調査する.
- 免疫反応と病原体抵抗に対する代謝物質誘発のデンドライト突起の影響を決定する.
主な方法:
- マウスの腸内CX3CR1+細胞に対する細菌代謝産物 (ピルビック酸,乳酸) の影響を調査した.
- GPR31欠乏したマウス (Gpr31b-/-) を利用して,受容体の役割を評価した.
- 特定病原体と細菌のないマウスの小腸の分析
- ワイルド型とGpr31b-/ - マウスを経口投与した.
- Salmonella Typhimurium感染に対する免疫反応と耐性を評価した.
主要な成果:
- ピルビック酸と乳酸は,GPR31経由でCX3CR1+細胞のデンドライト突起を誘発する主要な細菌代謝物質として特定されました.
- GPR31が欠けているマウスは 欠陥のあるデンドライトの突起を示した.
- 乳酸とピルバートの経口投与は,野生型のマウスではデンドライトの突起を強めたが,Gpr31b-/ - マウスではそうではなかった.
- 乳酸またはピルバートの治療は,野生型のマウスの免疫反応とサルモネラ耐性を著しく高めました.
結論:
- 腸内細菌によって生成される乳酸とピルバートは,腸内CX3CR1+細胞のGPR31媒介のデンドライト突起を誘導する.
- このメカニズムは免疫反応を強化し サルモネラなどの腸内感染症に対する抵抗力を提供します
- 細菌の代謝産物と腸内免疫系の抗原採取能力の間の直接的なリンクを強調しています.
関連する概念動画
Bacterial Flora of the Large Intestine
1.7K
The gut microbiome is formed by a vast and diverse community of bacteria that colonizes our large intestine. These bacteria start residing in the gut from birth and continue diversifying throughout life, influenced by factors such as diet, lifestyle, and stress. The gut bacterial community also includes bacteria from food and those that enter the colon through the anus.
The normal gut flora of the colon plays a critical role in generating essential vitamins such as vitamins K, B5, and B7.
The normal gut flora of the colon plays a critical role in generating essential vitamins such as vitamins K, B5, and B7.
1.7K
Types of Membrane Protrusions
3.7K
The protrusion of the cell surface is an initial step for several cellular processes, including cell migration, phagocytosis, and neurite outgrowth. These membrane protrusions are a result of cytoskeletal rearrangement. The most widely observed cell protrusions include lamellipodia, pseudopodia, filopodia, microvilli, invadopodia, and podosomes. These protrusions can be of two types — static or dynamic.
The microvilli, an example of stable protrusions, are finger-like projections...
The microvilli, an example of stable protrusions, are finger-like projections...
3.7K
Anatomy of the Intestines
87.4K
Although digestion of proteins, carbohydrates, and lipids may begin in the stomach, it is completed in the intestine. The absorption of nutrients, water, and electrolytes from food and drink also occurs in the intestine. The intestines can be divided into two structurally distinct organs—the small and large intestines.
Small Intestines
The small intestine is an ~7 meter-long tube with an inner diameter of just 2.5 cm. Since most nutrients are absorbed here, the inner lining of the...
Small Intestines
The small intestine is an ~7 meter-long tube with an inner diameter of just 2.5 cm. Since most nutrients are absorbed here, the inner lining of the...
87.4K
Neurons: The Cell Body and the Dendrites
7.1K
A typical nerve cell comprises three main components: the cell body, dendrites, and the axon. The cell body, also known as the soma or perikaryon, serves as the central biosynthetic hub housing a nucleus surrounded by cytoplasm containing organelles commonly found in most cells. Notably, Nissl bodies, clusters of the rough endoplasmic reticulum and free ribosomes responsible for protein synthesis, are distinctive features of the neuronal cell body. As neurons age, aggregates of a brown pigment...
7.1K
Renewal of Intestinal Stem Cells
3.2K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
3.2K
Frequency-dependent Selection
23.9K
When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
23.9K


