A Mouse Model of Mild <i>Clostridioides difficile</i> Infection for the Characterization of Natural Immune Responses
(1) Background: We describe a model of primary mild-<i>Clostridioides difficile</i> infection (CDI) in a naïve host, including gut microbiota analysis, weight loss, mortality, length of colonization. This model was used in order to describe the kinetics of humoral (IgG, IgM) and mucosal...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-09-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/12/10/1933 |
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| Summary: | (1) Background: We describe a model of primary mild-<i>Clostridioides difficile</i> infection (CDI) in a naïve host, including gut microbiota analysis, weight loss, mortality, length of colonization. This model was used in order to describe the kinetics of humoral (IgG, IgM) and mucosal (IgA) immune responses against toxins (TcdA/TcdB) and surface proteins (SlpA/FliC). (2) Methods: A total of 10<sup>5</sup> CFU vegetative forms of <i>C. difficile</i> 630Δ<i>erm</i> were used for challenge by oral administration after dysbiosis, induced by a cocktail of antibiotics. Gut microbiota dysbiosis was confirmed and described by 16S rDNA sequencing. We sacrificed C57Bl/6 mice after different stages of infection (day 6, 2, 7, 14, 21, 28, and 56) to evaluate IgM, IgG against TcdA, TcdB, SlpA, FliC in blood samples, and IgA in the cecal contents collected. (3) Results: In our model, we observed a reproducible gut microbiota dysbiosis, allowing for <i>C. difficile</i> digestive colonization. CDI was objectivized by a mean weight loss of 13.1% and associated with a low mortality rate of 15.7% of mice. We observed an increase in IgM anti-toxins as early as D7 after challenge. IgG increased since D21, and IgA anti-toxins were secreted in cecal contents. Unexpectedly, neither anti-SlpA nor anti-FliC IgG or IgA were observed in our model. (4) Conclusions: In our model, we induced a gut microbiota dysbiosis, allowing a mild CDI to spontaneously resolve, with a digestive clearance observed since D14. After this primary CDI, we can study the development of specific immune responses in blood and cecal contents. |
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| ISSN: | 2076-2607 |