Splenic Damage during SIV Infection: Role of T-Cell Depletion and Macrophage Polarization and Infection

Dionna W. Williams, Elizabeth L. Engle, Erin N. Shirk, Suzanne E. Queen, Lucio Gama, Joseph L. Mankowski, M. Christine Zink, Janice E. Clements

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of HIV infection on spleen and its cellular subsets have not been fully characterized, particularly for macrophages in which diverse populations exist. We used an accelerated SIV-infected macaque model to examine longitudinal effects on T-cell and macrophage populations and their susceptibilities to infection. Substantial lymphoid depletion occurred, characterized by follicular burn out and a loss of CD3 T lymphocytes, which was associated with cellular activation and transient dysregulations in CD4/CD8 ratios and memory effector populations. In contrast, the loss of CD68 and CD163+CD68+ macrophages and increase in CD163 cells was irreversible, which began during acute infection and persisted until terminal disease. Mac387 macrophages and monocytes were transiently recruited into spleen, but were not sufficient to mitigate the changes in macrophage subsets. Type I interferon, M2 polarizing genes, and chemokine-chemokine receptor signaling were up-regulated in spleen and drove macrophage alterations. SIV-infected T cells were numerous within the white pulp during acute infection, but were rarely observed thereafter. CD68, CD163, and Mac387 macrophages were highly infected, which primarily occurred in the red pulp independent of T cells. Few macrophages underwent apoptosis, indicating that they are a long-lasting target for HIV/SIV. Our results identify macrophages as an important contributor to HIV/SIV infection in spleen and in promoting morphologic changes through the loss of specific macrophage subsets that mediate splenic organization.

Original languageEnglish (US)
Pages (from-to)2068-2087
Number of pages20
JournalAmerican Journal of Pathology
Volume186
Issue number8
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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