Figure 8.

Schematic representation of changes in macrophage populations in spleen during longitudinal SIV infection. During homeostasis in the uninfected spleen, CD68 and CD163⁺CD68⁺ cells represent the predominant macrophage subsets in the germinal center and red pulp, respectively. Although relatively devoid of macrophages, the mantle zone (M) primarily consists of CD68 and Mac387 cells. There are numerous CD68, CD163⁺CD68⁺, and Mac387 cells in the macrophage-rich marginal zone (MZ). Within this area of the spleen, the CD68 cells reside in closer proximity to the mantle zone, whereas the CD163⁺CD68⁺ macrophages are proximal to the red pulp. Macrophages undergo changes in polarization and substantially alter their expression of cell markers after SIV infection. During the acute phase of infection, there is a global up-regulation of CD163 throughout the entire spleen. In contrast, there is a simultaneous and substantial decrease in CD68 macrophages. In addition, CD163 and Mac387 cells replace the fetal-derived CD163⁺CD68⁺ macrophages in the red pulp in the acute phase. During asymptomatic infection, peripheral blood monocytes are recruited into the spleen and rapidly disseminate to the germinal center. A limited recovery of CD68 macrophages in the mantle and marginal zones happens during this time. The dysregulation of mantle zone, marginal zone, and red pulp macrophages are maintained during chronic and late-stage infection. Notably during this late time, CD163⁺CD68⁺ macrophages become present in the germinal center, perhaps as a final compensatory mechanism in an effort to recover the CD68 cells that were lost acutely. Therefore, macrophages are altered in every area of the spleen during SIV infection, and never fully recover to the previous state found in uninfected animals.