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Increased inherent intestinal granzyme B expression may be associated with SIV pathogenesis in Asian non-human primates
Authors:Hutchison A T  Schmitz J E  Miller C J  Sastry K J  Nehete P N  Major A M  Ansari A A  Tatevian N  Lewis D E
Affiliation:University of Texas Health Science Center-Medical School at Houston, Division of Infectious Diseases, Department of Internal Medicine, Houston, 77030, USA. Alexander.T.Hutchison@uth.tmc.edu
Abstract:Background Unlike Asian non‐human primates, chronically SIV‐infected African non‐human primates (NHP) display a non‐pathogenic disease course. The different outcomes may be related to the development of an SIV‐mediated breach of the intestinal mucosa in the Asian species that is absent in the African animals. Methods To examine possible mechanisms that could lead to the gut breach, we determined whether the colonic lamina propria (LP) of SIV‐naïve Asian monkeys contained more granzyme B (GrB) producing CD4 T cells than did that of the African species. GrB is a serine protease that may disrupt mucosal integrity by damaging tight junction proteins. Results We found that the colonic LP of Asian NHP contain more CD4+/GrB+ cells than African NHP. We also observed reduced CD4 expression on LP T cells in African green monkeys. Conclusion Both phenotypic differences could protect against SIV‐mediated damage to the intestinal mucosa and could lead to future therapies in HIV+ humans.
Keywords:colon  Immune activation  microbial translocation  mucosal epithelium  tight junctions
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