Macrophages regulate gastrointestinal motility through complement component 1q
- The University of Texas Southwestern Medical Center, United States
Abstract
Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for immune defense of the intestine. Instead, C1q-expressing macrophages were located in the intestinal submucosal and myenteric plexuses where they closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased neurogenic activity of peristalsis, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.
Data availability
16S rRNA gene sequencing data (Figure 3D) and RNA sequencing data (Figure 6A and B; Figure 1 - figure supplement 1; Figure 6 - figure supplement 3) are available from the Sequence Read Archive under BioProject ID PRJNA793870. All mouse strains used are available commercially.
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Macrophages control gastrointestinal motility through complement component 1qSequence Read Archive; PRJNA793870.
Article and author information
Author details
Alexander A Crofts
Funding
National Institutes of Health (R01 DK070855)
- Lora V Hooper
Welch Foundation Grant (I-1874)
- Lora V Hooper
Howard Hughes Medical Institute (N/A)
- Lora V Hooper
National Institutes of Health (T32 AI005284)
- Mihir Pendse
National Institutes of Health (T32 AI005284)
- Alexander A Crofts
National Institutes of Health (F32 DK132913)
- Alexander A Crofts
National Institutes of Health (F31 DK126391)
- Eugene Koo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Isaac M Chiu, Harvard Medical School, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (protocol #2015-101212) of the University of Texas Southwestern Medical Center.
Version history
- Preprint posted: January 28, 2022 (view preprint)
- Received: March 11, 2022
- Accepted: April 17, 2023
- Accepted Manuscript published: April 26, 2023 (version 1)
- Version of Record published: May 15, 2023 (version 2)
Copyright
© 2023, Pendse et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Macrophages regulate gastrointestinal motility through complement component 1q
eLife 12:e78558.
https://doi.org/10.7554/eLife.78558
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