Chris Peritore-Galve
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fcperitore.bsky.social
Chris Peritore-Galve
@fcperitore.bsky.social
73 followers 130 following 21 posts
Postdoc in the Borden Lacy Lab at Vanderbilt University Medical Center | Incoming Assistant Professor at The Ohio State University | Professional 🦠and 💩 aficionado | Non-professional 🪴🐶🐦 enthusiast| 🇲🇽 🇺🇸 |
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fcperitore.bsky.social
15/20 The lack of outward signs of disease and limited histopathology was curious, so we tested this with additional TcdB3+ strains and found that the mild disease with edema + inflammation being the most informative markers was consistent across ribotype 017 strains.
Hematoxylin and eosin-stained ceca of mice infected with three independent C. difficile strains encoding TcdB3. There is little to no damage to the epithelial layer and the only appreciable pathology is severe edema and inflammatory infiltrate.
November 7, 2025 at 7:11 PM
fcperitore.bsky.social
14/20 Mice infected with the TcdB3+ strain develop no appreciable epithelial damage, but they do exhibit high amounts of inflammation and edema. Surprisingly, even though AZD5148 did not neutralize TcdB3 in vitro, it significantly protected against the inflammation and edema phenotypes in vivo!
Hematoxylin and eosin-stained ceca of mice prophylactically administered antibodies, then infected with the TcdB3-encoding strain M68. Columns left-to right are: healthy control, isotype IgG control, 0.5 mg/kg AZD5148, 1 mg/kg AZD5148, 0.5 mg/kg bezlotoxumab, and 1 mg/kg bezlotoxumab. The healthy tissue has nicely formed crypts, not much space between the mucosa and the seromuscular layer, indicating that there is no edema. The control IgG group has significant expansion of the submucosa and inflammatory cells in this compartment as well as an expansion of gut-associated lymphoid tissue. The 0.5 mg/kg AZD5148 cecum images have less submucosal edema and inflammatory infiltrates compared to the control IgG group, but the 1 mg/kg AZD5148 images are near healthy. In contrast, both 0.5 and 1 mg/kg groups of bezlotoxumab have significant amounts of edema and inflammatory infiltrates.
November 7, 2025 at 7:11 PM
fcperitore.bsky.social
11/20 What is baffling is that despite protecting against lethality and weight loss, mAb therapy did not have an impact on pathology. This could be due to systemic effects of neutralizing TcdB, or the prevention of further damage by directing more AZD5148 from the bloodstream to the tissue, or more.
Hematoxylin and eosin staining of mouse cecum tissues prophylactically treated with anti-TcdB monoclonal antibodies or an isotype control. Columns left to right are control IgG, AZD5148, and Bezlotoxumab, all given at a dose of 2.5 mg/kg. The top row is a zoomed-out view showing a cross-section of the mouse ceca. There is a massive submucosal expansion, indicative of edema, and severe shedding of the epithelial layer. The bottom row shows a close-up image of the epithelium, which is highly inflamed, and is highly damaged and eroded in some areas.
November 7, 2025 at 7:11 PM