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Therapeutic Mechanism of Macrophage Inflammatory Protein 1 α Neutralizing Antibody (CCL3) in Clostridium difficile Infection in Mice
- Source :
- J Infect Dis
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Background Clostridium difficile infection (CDI) causes diarrhea and colitis. We aimed to find a common pathogenic pathway in CDI among humans and mice by comparing toxin-mediated effects in human and mouse colonic tissues. Method Using multiplex enzyme-linked immunosorbent assay, we determined the cytokine secretion of toxin A– and B–treated human and mouse colonic explants. Results Toxin A and toxin B exposure to fresh human and mouse colonic explants caused different patterns of cytokine secretion. Toxin A induced macrophage inflammatory protein (MIP) 1α secretion in both human and mouse explants. Toxin A reduced the expression of chloride anion exchanger SLC26A3 expression in mouse colonic explants and human colonic epithelial cells. Patients with CDI had increased colonic MIP-1 α expression and reduced colonic SLC26A3 (solute carrier family 26, member 3) compared with controls. Anti–MIP-1 α neutralizing antibody prevented death, ameliorated colonic injury, reduced colonic interleukin 1β (IL-1β) messenger RNA expression, and restored colonic SLC26a3 expression in C. difficile–infected mice. The anti–MIP-1 α neutralizing antibody prevented CDI recurrence. SLC26a3 inhibition augmented colonic IL-1 β messenger RNA expression and abolished the protective effect of anti–MIP-1 α neutralizing antibody in mice with CDI. Conclusion MIP-1 α is a common toxin A–dependent chemokine in human and mouse colon. MIP-1 α mediates detrimental effects by reducing SLC26a3 and enhancing IL-1 β expression in the colon.
- Subjects :
- 0301 basic medicine
Chemokine
Colon
Bacterial Toxins
Interleukin-1beta
030106 microbiology
Down-Regulation
CCL3
Clostridium difficile toxin A
Clostridium difficile toxin B
Enterotoxins
Mice
Major Articles and Brief Reports
03 medical and health sciences
medicine
Animals
Humans
Immunology and Allergy
Chloride-Bicarbonate Antiporters
RNA, Messenger
Colitis
Neutralizing antibody
Macrophage inflammatory protein
Chemokine CCL3
biology
Clostridioides difficile
Chemistry
Macrophage Inflammatory Proteins
medicine.disease
Antibodies, Neutralizing
Molecular biology
030104 developmental biology
Infectious Diseases
Gene Expression Regulation
Sulfate Transporters
Clostridium Infections
biology.protein
Cytokine secretion
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 221
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....39059b2b06eb86af74400dbcc12b6789