Loss of mucosal CD103 DCs and IL-17 and IL-22 lymphocytes is associated with mucosal damage in SIV infection

N. R. Klatt, J. D. Estes, X. Sun, A. M. Ortiz, J. S. Barber, L. D. Harris, B. Cervasi, L. K. Yokomizo, L. Pan, C. L. Vinton, B. Tabb, L. A. Canary, Q. Dang, V. M. Hirsch, G. Alter, Y. Belkaid, J. D. Lifson, G. Silvestri, J. D. Milner, M. PaiardiniE. K. Haddad, J. M. Brenchley

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV) disease progression is associated with multifocal damage to the gastrointestinal tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation, but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that microarray analysis showed expressed genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103 dendritic cells (DCs) after SIV infection, which associated with the loss of IL-17-and IL-22-producing lymphocytes. CD103 DCs expressed genes associated with promotion of IL-17/IL-22 cells, and coculture of CD103 DCs and naïve T cells led to increased IL17A and RORc expression in differentiating T cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis.

Original languageEnglish (US)
Pages (from-to)646-657
Number of pages12
JournalMucosal Immunology
Issue number6
StatePublished - Nov 2012
Externally publishedYes

Bibliographical note

Funding Information:
We would like to acknowledge Heather Cronise, JoAnne Swerczek, Richard Herbert, and all the veterinary staff at the NIH animal center. We would like to thank Tracy Meeker and Stephanie Ehnert, and the veterinary staff at YNPRC. We would like to thank the Cleveland Immunopathogenesis Consortium (BBC / CLIC) for advice and helpful discussions. We would like to thank Mark Cameron and Peter Wilkinson from the Genomics core at VGTI-FL for gene array consultation. Histology support was provided by the Pathology / Histotechnology Laboratory (PHL) core service located at the National Cancer Institute-Frederick, Frederick, MD, USA. These studies were supported by the Intramural National Institute of Allergy and Infectious Diseases, US National Institutes of Health program, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and National Institutes of Health R01 AI-084836 under M Paiardini. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States.


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