Fig. 6.3.

DC frequency, distribution, and functionality during pathogenic and nonpathogenic SIV infection. Early and sustained changes in pDC and mDC numbers, phenotype, tissue distribution, and function are attributable to pathogenic SIV infection. SIV infection is associated with an activated/mature pDC phenotype and semi-mature mDC phenotype. SIV infection induces the regulatory molecule B7-H1, CCR7, and α4β7 integrin expression by blood DCs that leads to recruitment of cells to lymphoid tissues in a CCR7-dependent manner and to intestinal mucosa in an α4β7-dependent manner. The changes in DC phenotype and increased migration into lymphoid tissues and mucosa seen in pathogenic SIV infections do not occur in natural SIV hosts. Robust immune activation is evident in pathogenic and nonpathogenic SIV hosts. However, nonpathogenic hosts express factors antagonizing IFN activity and suppressing ISGs (i.e., tryptophan-depleting enzyme indoleamine 2,3 dioxygenase (IDO), an adenosine deaminase that suppresses ISG expression (ADAR)). Only nonpathogenic SIV hosts downmodulate their responses in the chronic phase of disease