Pigtail macaques (PTMs) rapidly progress to AIDS after simian immunodeficiency virus (SIV) infection. Given the strong association between human immunodeficiency virus (HIV) and SIV disease progression and microbial translocation and immune activation, we assessed whether high basal levels of immune activation and microbial translocation exist in PTMs. We found that before SIV infection, PTMs had high levels of microbial translocation that correlated with significant damage to the structural barrier of the gastrointestinal tract. Moreover, this increased microbial translocation correlated with high levels of immune activation and was associated with high frequencies of interleukin-17-producing T cells. These data highlight the relationship among mucosal damage, microbial translocation and systemic immune activation in the absence of SIV replication, and underscore the importance of microbial translocation in the rapid course of disease progression in SIV-infected PTMs. Furthermore, these data suggest that PTM may be an ideal model to study therapeutic interventions aimed at decreasing microbial translocation-induced immune activation.
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We would like to acknowledge JoAnne Swerczek, Heather Cronise-Santis, Richard Herbert, and all the veterinary staff at the NIH animal center. We would like to thank the Bad Boys of Cleveland (BBC) for advice and helpful discussions. We would like to thank Jon Meddings, Marie Claire Arrieta, and Kyung Park at the University of Alberta and Coreen Beaumier at Walter Reed Medical center for technical support. Judith A Briant is funded by the Howard Hughes Medical Institute Research Scholars Program. These studies were supported by the Intramural National Institute of Allergy and Infectious Diseases, US National Institutes of Health program. This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E.