In Vitro Exposure to Prostratin but Not Bryostatin-1 Improves Natural Killer Cell Functions Including Killing of CD4+ T Cells Harboring Reactivated Human Immunodeficiency Virus

Frontiers in Immunology
Maria Giovanna DesimioMargherita Doria

Abstract

In the attempt of purging the HIV-1 reservoir through the "shock-and-kill" strategy, it is important to select latency-reversing agents (LRAs) devoid of deleterious effects on the antiviral function of immune effector cells. Here, we investigated two LRAs with PKC agonist activity, prostratin (PRO) and bryostatin-1 (BRY), for their impact on the function of natural killer (NK) cells, the major effectors of innate immunity whose potential in HIV-1 eradication has emerged in recent clinical trials. Using NK cells of healthy donors, we found that exposure to either PRO or BRY potently activated NK cells, resulting in upmodulation of NKG2D and NKp44 activating receptors and matrix metalloprotease-mediated shedding of CD16 receptor. Despite PRO and BRY affected NK cell phenotype in the same manner, their impact on NK cell function was diverse and showed considerable donor-to-donor variation. Altogether, in most tested donors, the natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) of NK cells were either improved or maintained by PRO, while both activities were impaired by BRY. Moreover, we analyzed the effect of these drugs on the capacity of treated NK cells to kill autologous latently infected CD4+ T cells re...Continue Reading

References

Jan 21, 1992·Journal of Immunological Methods·J BryantR B Herberman
Jan 1, 1988·International Journal of Immunopharmacology·M ItoS Shigeta
Jan 31, 2002·Annual Review of Medicine·Joel N BlanksonRobert F Siliciano
May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Livio AzzoniLuis J Montaner
Dec 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Domenico MavilioAnthony S Fauci
Jul 31, 2004·The Journal of Biological Chemistry·Samuel A WilliamsWarner C Greene
Mar 18, 2005·Annual Review of Immunology·Lewis L Lanier
Oct 22, 2005·Nature Reviews. Immunology·Anthony S FauciShyam Kottilil
Apr 22, 2008·Nature Immunology·Eric VivierSophie Ugolini
Jan 13, 2009·The Journal of Biological Chemistry·Xavier ContrerasB Matija Peterlin
Feb 10, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juan I AguilóAlberto Anel
Jul 15, 2011·Trends in Immunology·Jürgen SchellerStefan Rose-John
Nov 16, 2011·Immunology and Cell Biology·Fiona WightmanSharon R Lewin
Apr 6, 2012·The New England Journal of Medicine·Barton F HaynesJerome H Kim
Apr 14, 2012·Advances in Virology·Lisa N McKernanJoseph Kulkosky
Jun 30, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gregor F LichtfussAnthony Jaworowski
Jul 28, 2012·Nature·Steven G Deeks
Feb 12, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Giulia MatusaliMargherita Doria
Jun 19, 2013·Immunological Reviews·Nichole R KlattSteven G Deeks
Sep 17, 2013·Pharmaceutical Biology·Peter KollárJiří Pazourek
Dec 18, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurie LajoieGilles Thibault

❮ Previous
Next ❯

Citations

Sep 14, 2019·International Journal of Molecular Sciences·Maria G DesimioMargherita Doria
Sep 10, 2020·Frontiers in Cellular and Infection Microbiology·Wenli MuScott G Kitchen
Mar 16, 2021·Molecular Therapy. Nucleic Acids·Saikat Boliar, David G Russell
Jun 15, 2021·Frontiers in Immunology·Jingyi DingYu Lai
Jul 9, 2021·Journal of the International AIDS Society·Margherita DoriaUNKNOWN EPIICAL consortium
Aug 1, 2021·International Immunopharmacology·Jiawei JiXiaodong Zhang
Dec 12, 2018·ACS Infectious Diseases·Nizar Mohammad AbuharfeilFawzi M Alsheyab
Nov 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Seeseei Molimau-SamasoniAndrew B Munkacsi

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
GAM
PCR
flow cytometry
PMA
ELISA
gene array

Software Mentioned

GraphPad Prism
Flow Jo
Tree Star

Related Concepts

Related Feeds

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex, associated with a generally dismal prognosis owing to its aggressive behavior. Here are the latest discoveries pertaining to this disease.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.