Marked Enteropathy in an Accelerated Macaque Model of AIDS

Joshua D. Croteau, Elizabeth L. Engle, Suzanne E. Queen, Erin N. Shirk, Mary Christine Zink

Research output: Contribution to journalArticle

Abstract

Enteropathy in HIV infection is not eliminated with combination antiretroviral therapy and is possibly linked to microbial translocation. We used a rapidly progressing SIV/pigtailed macaque model of HIV to examine enteropathy and microbial translocation. Histologic evidence of intestinal disease was observed in only half of infected macaques during late-stage infection (LSI). Combination antiretroviral therapy initiated during acute infection prevented intestinal disease. In the ileum and colon, enteropathy was associated with increased caspase-3 staining, decreased CD3+ T cells, and increased SIV-infected cells. CD3+ T cells were preserved in LSI animals without intestinal disease, and levels of CD3 staining in all LSI animals strongly correlated with the number of infected cells in the intestine and plasma viral load. Unexpectedly, there was little evidence of microbial translocation as measured by soluble CD14, soluble CD163, lipopolysaccharide binding protein, and microbial 16s ribosomal DNA. Loss of epithelial integrity indicated by loss of the tight junction protein claudin-3 was not observed during acute infection despite significantly fewer T cells. Claudin-3 was reduced in LSI animals with severe intestinal disease but did not correlate with increased microbial translocation. LSI animals that did not develop intestinal disease had increased T-cell intracytoplasmic antigen 1–positive cytotoxic T lymphocytes, suggesting a robust adaptive cytotoxic T-lymphocyte response may, in part, confer resilience to SIV-induced intestinal damage.

Original languageEnglish (US)
Pages (from-to)589-604
Number of pages16
JournalAmerican Journal of Pathology
Volume187
Issue number3
DOIs
StatePublished - Mar 1 2017

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Macaca
Intestinal Diseases
Acquired Immunodeficiency Syndrome
Infection
Claudin-3
T-Lymphocytes
Cytotoxic T-Lymphocytes
Staining and Labeling
Tight Junction Proteins
Ribosomal DNA
Viral Load
Ileum
Caspase 3
HIV Infections
Intestines
Colon
Cell Count
HIV
Antigens
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Marked Enteropathy in an Accelerated Macaque Model of AIDS. / Croteau, Joshua D.; Engle, Elizabeth L.; Queen, Suzanne E.; Shirk, Erin N.; Zink, Mary Christine.

In: American Journal of Pathology, Vol. 187, No. 3, 01.03.2017, p. 589-604.

Research output: Contribution to journalArticle

Croteau, Joshua D. ; Engle, Elizabeth L. ; Queen, Suzanne E. ; Shirk, Erin N. ; Zink, Mary Christine. / Marked Enteropathy in an Accelerated Macaque Model of AIDS. In: American Journal of Pathology. 2017 ; Vol. 187, No. 3. pp. 589-604.
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