KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques

Published on 2017-07-14T17:51:38Z (GMT) by
<div><p>Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01<sup>+</sup> and KIR3DL05<sup>+</sup> macaques with and without defined ligands for these receptors with SIV<sub>mac</sub>239, and monitored NK cell responses in peripheral blood and lymphoid tissues. NK cell responses in blood were broadly stimulated, as indicated by rapid increases in the CD16<sup>+</sup> population during acute infection and sustained increases in the CD16<sup>+</sup> and CD16<sup>-</sup>CD56<sup>-</sup> populations during chronic infection. Markers of proliferation (Ki-67), activation (CD69 & HLA-DR) and antiviral activity (CD107a & TNFα) were also widely expressed, but began to diverge during chronic infection, as reflected by sustained CD107a and TNFα upregulation by KIR3DL01<sup>+</sup>, but not by KIR3DL05<sup>+</sup> NK cells. Significant increases in the frequency of KIR3DL01<sup>+</sup> (but not KIR3DL05<sup>+</sup>) NK cells were also observed in tissues, particularly in the gut-associated lymphoid tissues, where this receptor was preferentially upregulated on CD56<sup>+</sup> and CD16<sup>-</sup>CD56<sup>-</sup> subsets. These results reveal broad NK cell activation and dynamic changes in the phenotypic properties of NK cells in response to SIV infection, including the enrichment of KIR3DL01<sup>+</sup> NK cells in tissues that support high levels of virus replication.</p></div>

Cite this collection

Ries, Moritz; R. Reynolds, Matthew; Bashkueva, Ksenia; Crosno, Kristin; Capuano, Saverio; Prall, Trent M.; Wiseman, Roger; H. O’Connor, David; G. Rakasz, Eva; Uno, Hajime; D. Lifson, Jeffrey; T. Evans, David (2017): KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques. PLOS Pathogens.

https://doi.org/10.1371/journal.ppat.1006506

Retrieved: 14:56, Nov 24, 2017 (GMT)