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TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection

Toll-like receptors (TLRs) play a crucial role in innate immunity and provide a first line of host defense against invading pathogens. Of the identified human TLRs, TLR10 remains an orphan receptor whose ligands and functions are poorly understood. In the present study, we sought to evaluate the lev...

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Autores principales: Henrick, Bethany M., Yao, Xiao-Dan, Zahoor, Muhammad Atif, Abimiku, Alash'le, Osawe, Sophia, Rosenthal, Kenneth L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430187/
https://www.ncbi.nlm.nih.gov/pubmed/30930906
http://dx.doi.org/10.3389/fimmu.2019.00482
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author Henrick, Bethany M.
Yao, Xiao-Dan
Zahoor, Muhammad Atif
Abimiku, Alash'le
Osawe, Sophia
Rosenthal, Kenneth L.
author_facet Henrick, Bethany M.
Yao, Xiao-Dan
Zahoor, Muhammad Atif
Abimiku, Alash'le
Osawe, Sophia
Rosenthal, Kenneth L.
author_sort Henrick, Bethany M.
collection PubMed
description Toll-like receptors (TLRs) play a crucial role in innate immunity and provide a first line of host defense against invading pathogens. Of the identified human TLRs, TLR10 remains an orphan receptor whose ligands and functions are poorly understood. In the present study, we sought to evaluate the level of TLR10 expression in breast milk (BM) and explore its potential function in the context of HIV-1 infection. We evaluated HIV-1-infected (Nigerian: n = 40) and uninfected (Nigerian: n = 27; Canadian: n = 15) BM samples for TLR expression (i.e., TLR10, TLR2, and TLR1) and report here that HIV-1-infected BM from Nigerian women showed significantly higher levels of TLR10, TLR1, and TLR2 expression. Moreover, the level of TLR10 expression in HIV-1-infected BM was upregulated by over 100-fold compared to that from uninfected control women. In vitro studies using TZMbl cells demonstrated that TLR10 overexpression contributes to higher HIV-1 infection and proviral DNA integration. Conversely, TLR10 inhibition significantly decreased HIV-1 infection. Notably, HIV-1 gp41 was recognized as a TLR10 ligand, leading to the induction of IL-8 and NF-κBα activation. The identification of a TLR10 ligand and its involvement in HIV-1 infection enhances our current understanding of HIV-1 replication and may assist in the development of improved future therapeutic strategies.
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spelling pubmed-64301872019-03-29 TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection Henrick, Bethany M. Yao, Xiao-Dan Zahoor, Muhammad Atif Abimiku, Alash'le Osawe, Sophia Rosenthal, Kenneth L. Front Immunol Immunology Toll-like receptors (TLRs) play a crucial role in innate immunity and provide a first line of host defense against invading pathogens. Of the identified human TLRs, TLR10 remains an orphan receptor whose ligands and functions are poorly understood. In the present study, we sought to evaluate the level of TLR10 expression in breast milk (BM) and explore its potential function in the context of HIV-1 infection. We evaluated HIV-1-infected (Nigerian: n = 40) and uninfected (Nigerian: n = 27; Canadian: n = 15) BM samples for TLR expression (i.e., TLR10, TLR2, and TLR1) and report here that HIV-1-infected BM from Nigerian women showed significantly higher levels of TLR10, TLR1, and TLR2 expression. Moreover, the level of TLR10 expression in HIV-1-infected BM was upregulated by over 100-fold compared to that from uninfected control women. In vitro studies using TZMbl cells demonstrated that TLR10 overexpression contributes to higher HIV-1 infection and proviral DNA integration. Conversely, TLR10 inhibition significantly decreased HIV-1 infection. Notably, HIV-1 gp41 was recognized as a TLR10 ligand, leading to the induction of IL-8 and NF-κBα activation. The identification of a TLR10 ligand and its involvement in HIV-1 infection enhances our current understanding of HIV-1 replication and may assist in the development of improved future therapeutic strategies. Frontiers Media S.A. 2019-03-15 /pmc/articles/PMC6430187/ /pubmed/30930906 http://dx.doi.org/10.3389/fimmu.2019.00482 Text en Copyright © 2019 Henrick, Yao, Zahoor, Abimiku, Osawe, and Rosenthal. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Henrick, Bethany M.
Yao, Xiao-Dan
Zahoor, Muhammad Atif
Abimiku, Alash'le
Osawe, Sophia
Rosenthal, Kenneth L.
TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection
title TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection
title_full TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection
title_fullStr TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection
title_full_unstemmed TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection
title_short TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection
title_sort tlr10 senses hiv-1 proteins and significantly enhances hiv-1 infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430187/
https://www.ncbi.nlm.nih.gov/pubmed/30930906
http://dx.doi.org/10.3389/fimmu.2019.00482
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