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Published on: May 2, 2017
Influence of alemtuzumab on the intestinal Paneth cells and microflora in macaques
Qiurong Li1, Qiang Zhang, Chenyang Wang
1Research Institute of General Surgery, Jinling Hospital, Nanjing 210002, China; School of Medicine, Nanjing University, Nanjing 210093, China. liqiurong@yahoo.com
Abstract:
Alemtuzumab has been recently introduced for induction therapy in organ transplantation. However, the pathogenesis and molecular mechanism of the impact of such induction therapy on bacterial infections remain to be clarified. We found the alterations of Paneth cells including abnormal Paneth cell granules and expression of lysozyme and defensin 5 in response to lymphocyte depletion by alemtuzumab. Lymphocyte depletion resulted in decreased expression of TNF-alpha, IFN-gamma, IL-10 and TGF-beta in the intestine. The diversity of gut bacteria varied significantly between different times of alemtuzumab treatment. Abnormal expression of granule peptides might result in impairment of host gut microflora. The alterations in bacterial microflora had almost reversed 56days after alemtuzumab treatment, which was consistent with our results that Paneth cells were recovered to secrete antimicrobial peptides to govern gut microflora. These findings indicated the associations between changes of Paneth cell function and gut microflora and supported the important role of Paneth cells to barrier impairment with the use of alemtuzumab in organ transplantation.
Insights
Alemtuzumab induction therapy alters gut bacteria by affecting Paneth cells, crucial for immune defense. Gut microflora diversity and Paneth cell function recover over time post-treatment.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Alemtuzumab is used for induction therapy in organ transplantation.
- The impact of alemtuzumab on bacterial infections and its underlying mechanisms are not fully understood.
Purpose of the Study:
- To investigate the effects of alemtuzumab-induced lymphocyte depletion on Paneth cells and gut microbiota.
- To elucidate the molecular mechanisms linking alemtuzumab therapy to changes in gut barrier function and infection susceptibility.
Main Methods:
- Analysis of Paneth cell morphology and expression of antimicrobial peptides (lysozyme, defensin 5).
- Measurement of intestinal cytokine expression (TNF-alpha, IFN-gamma, IL-10, TGF-beta).
- Assessment of gut bacterial diversity using sequencing techniques at various time points during alemtuzumab treatment.
Main Results:
- Alemtuzumab treatment led to abnormal Paneth cell granules and altered expression of lysozyme and defensin 5.
- Lymphocyte depletion decreased key intestinal cytokine levels.
- Significant variations in gut bacterial diversity were observed during treatment, correlating with Paneth cell dysfunction.
- Gut microbiota and Paneth cell function showed signs of recovery approximately 56 days post-treatment.
Conclusions:
- Alemtuzumab-induced lymphocyte depletion impacts Paneth cell function and gut microbiota composition.
- Dysfunctional Paneth cells may impair host defense against bacterial infections during alemtuzumab therapy.
- Paneth cells play a critical role in maintaining gut barrier integrity and microbial homeostasis, particularly in the context of alemtuzumab treatment in organ transplantation.
