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| Status |
Public on Jan 16, 2024 |
| Title |
Gut complement induced by the microbiota combats pathogens and spares commensals |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization, is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host’s specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as a novel innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.
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| Overall design |
To identify which intestinal cell types express C3 under homeostasis, we used single-cell RNASeq (scRNASeq) to perform a transcriptional survey of C3 expression across intestinal populations. We isolated C3-expressing cells (tdTomato-positive) from the subepithelial compartment of both male and female C3IRES-tdTomato C57BL/6 mice and performed scRNASeq on these cells.
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| Contributor(s) |
Meng W, Ian M |
| Citation(s) |
38280374 |
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| Submission date |
Dec 15, 2023 |
| Last update date |
Feb 06, 2024 |
| Contact name |
CBDM Lab |
| E-mail(s) |
cbdm@hms.harvard.edu
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| Phone |
617-432-7747
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| Organization name |
Harvard Medical School
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| Department |
Microbiology and Immunobiology
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| Lab |
CBDM
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| Street address |
77 Avenue Louis Pasteur
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA1053274 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE250268_RAW.tar |
58.8 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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