Nonpathogenic <scp>SIV</scp> Infection in Sooty Mangabeys Is Characterized by a Lack of Activation and Expansion of Monocytes

ABSTRACT Introduction Natural hosts of simian immunodeficiency virus (SIV), including sooty mangabeys (SMs), maintain high viremia without progressing to AIDS and AIDS‐associated histopathogenesis. The mechanisms underlying this protection and lack of pathogenesis remain incompletely understood, particularly in relation to monocyte/macrophage activation. Methods Plasma soluble CD163 (sCD163), monocyte CD163 expression, and monocyte subset phenotypes were quantified in uninfected and naturally SIV‐infected SMs and compared with uninfected and SIV‐infected rhesus macaques (RMs). Flow cytometry and multivariate analyses were used to assess monocyte activation and subset distribution. Results sCD163 levels and CD163 surface expression were increased in SIV‐infected RMs but not SMs. SIV‐infected SMs exhibited reduced CD14 + CD16 + monocyte expansion and lower expression of CD64, MAC387, CD11b, and CCR2 compared with SIV‐infected RMs. Machine learning identified CD14 + CD16 + CCR8 + monocytes as the top discriminator of SIV infection in SMs. Conclusion These findings indicate a lack of monocyte activation in SMs that correlates with non‐pathogenic infection.