TY - JOUR
T1 - Splenic Damage during SIV Infection
T2 - Role of T-Cell Depletion and Macrophage Polarization and Infection
AU - Williams, Dionna W.
AU - Engle, Elizabeth L.
AU - Shirk, Erin N.
AU - Queen, Suzanne E.
AU - Gama, Lucio
AU - Mankowski, Joseph L.
AU - Zink, M. Christine
AU - Clements, Janice E.
N1 - Publisher Copyright:
© 2016 American Society for Investigative Pathology
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2016.03.019
DO - 10.1016/j.ajpath.2016.03.019
M3 - Article
C2 - 27322772
AN - SCOPUS:84990063295
VL - 186
SP - 2068
EP - 2087
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 8
ER -