Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells
Chen Xiang,
Peihua Chen,
Qin Zhang,
Yinghui Li,
Ying Pan,
Wenchun Xie,
Jianyuan Sun,
Zhihua Liu
Affiliations
Chen Xiang
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Peihua Chen
University of Chinese Academy of Sciences, Beijing 100049, China; The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, CAS; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China; State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, CAS, Beijing, 100101, China
Qin Zhang
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Yinghui Li
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Ying Pan
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Wenchun Xie
Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Guang Dong Bio-healtech Advanced Co., Ltd., Foshan, 528000, P. R. China
Jianyuan Sun
University of Chinese Academy of Sciences, Beijing 100049, China; The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, CAS; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China; State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, CAS, Beijing, 100101, China; Corresponding author
Zhihua Liu
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Institute for Immunology, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China; Corresponding author
Summary: The intestinal microbiota closely interacts with the neuroendocrine system and exerts profound effects on host physiology. Here, we report that nucleotide-binding oligomerization domain 1 (Nod1) ligand derived from intestinal bacteria modulates catecholamine storage and secretion in mouse adrenal chromaffin cells. The cytosolic peptidoglycan receptor Nod1 is involved in chromogranin A (Chga) retention in dense core granules (DCGs) in chromaffin cells. Mechanistically, upon recognizing its ligand, Nod1 localizes to DCGs, and recruits Rab2a, which is critical for Chga and epinephrine retention in DCGs. Depletion of Nod1 ligand or deficiency of Nod1 leads to a profound defect in epinephrine storage in chromaffin cells and subsequently less secretion upon stimulation. The intestine-adrenal medulla cross talk bridged by Nod1 ligand modulates adrenal medullary responses during the immobilization-induced stress response in mice. Thus, our study uncovers a mechanism by which intestinal microbes modulate epinephrine secretion in response to stress, which may provide further understanding of the gut-brain axis.
