TY - JOUR
T1 - In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol
T2 - water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion
AU - Olwenyi, Omalla A.
AU - Asingura, Bannet
AU - Naluyima, Prossy
AU - Anywar, Godwin Upoki
AU - Nalunga, Justine
AU - Nakabuye, Mariam
AU - Semwogerere, Michael
AU - Bagaya, Bernard
AU - Cham, Fatim
AU - Tindikahwa, Allan
AU - Kiweewa, Francis
AU - Lichter, Eliezer Z.
AU - Podany, Anthony T.
AU - Fletcher, Courtney V.
AU - Byrareddy, Siddappa N.
AU - Kibuuka, Hannah
N1 - Funding Information:
OAO acknowledges grant support from GSK Trust in Africa. We highly appreciate all study participants for their willingness to participate in this study. Many thanks to Michael A. Eller and Julie Ake who not only pioneered and supported various T cell activation studies within our laboratories but also provided useful suggestions and constructive guidance during the design and formulation of this study.
Funding Information:
This research was supported by the GlaxoSmithKline (GSK) Trust in Africa research grant offered to OAO. In addition, OAO receives on-going support from the Fulbright Foreign Student Program. Both BA and PN received Global Health Travel Awards to present portions of these results at the joint meeting of HIV Vaccines and Functional Cures/ Eradication of HIV held at Fairmont Chateau Whistler, BC Canada on March 24–28, 2019. “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. Methods: Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. Results: Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups. Conclusion: A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.
AB - Background: In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. Methods: Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. Results: Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups. Conclusion: A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.
KW - Azadirachta indica (A. indica) ethanol: water mixture
KW - CD4 T cell activation/exhaustion
KW - Immunomodulation
KW - Microbial translocation
KW - Staphylococcal enterotoxin B (SEB)
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U2 - 10.1186/s12906-021-03288-0
DO - 10.1186/s12906-021-03288-0
M3 - Article
C2 - 33836748
AN - SCOPUS:85104117228
VL - 21
JO - BMC Complementary Medicine and Therapies
JF - BMC Complementary Medicine and Therapies
SN - 1472-6882
IS - 1
M1 - 114
ER -