Anna C. Hearps, Paul A. Agius, Jingling Zhou, Samantha Brunt, Mkunde Chachage, Thomas A. Angelovich, Paul U. Cameron, Michelle Giles, Patricia Price, Julian Elliott, Anthony Jaworowski
Abstract
Innate immune dysfunction persists in HIV(+) individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56(dim) NK cell population lacking the signal transducing protein FcRγ is expanded in HIV(+) individuals. Here, we analyzed a cohort of HIV(+) men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69(+)) and late (HLA-DR(+)/CD38(+)) activation were elevated in cART-naïve HIV(+) MSM (p = 0.004 and 0.015, respectively), as were FcRγ(-) NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ(-) NK cells (p = 0.115) or activated HLA-DR(+)/CD38(+) NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ(-) NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56(dim) FcRγ(-) NK cell expansion and immune activation in HIV(+) individuals. While proportions of activated CD69(+) NK cells declined significantly on cART (p = 0.003), the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56(dim) FcRγ(-) NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV(+) individuals on cART.
Pharmacology, Toxicology and Pharmaceutical Science
1
5%
Other
2
10%
Unknown
8
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 July 2017.
All research outputs
#15,279,596
of 26,414,132 outputs
Outputs from Frontiers in immunology
#13,079
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Outputs of similar age
#165,906
of 333,341 outputs
Outputs of similar age from Frontiers in immunology
#204
of 407 outputs
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So far Altmetric has tracked 33,172 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one has gotten more attention than average, scoring higher than 58% of its peers.
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