Influence of alemtuzumab on the intestinal Paneth cells and microflora in macaques

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-α, IFN-γ, IL-10 and TGF-β 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 56 days 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.