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TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads
BACKGROUND: LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788896/ https://www.ncbi.nlm.nih.gov/pubmed/26969150 http://dx.doi.org/10.1186/s12977-016-0248-y |
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author | Low, Hui Zhi Ahrenstorf, Gerrit Pommerenke, Claudia Habermann, Nadine Schughart, Klaus Ordóñez, David Stripecke, Renata Wilk, Esther Witte, Torsten |
author_facet | Low, Hui Zhi Ahrenstorf, Gerrit Pommerenke, Claudia Habermann, Nadine Schughart, Klaus Ordóñez, David Stripecke, Renata Wilk, Esther Witte, Torsten |
author_sort | Low, Hui Zhi |
collection | PubMed |
description | BACKGROUND: LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection. RESULTS: We analyzed a panel of TLR agonists and found that ssRNA40, a TLR8 agonist, is a potent inducer of LILRA3 in healthy individuals. However, this regulation is much diminished in HIV. Comparison of TLR8 to TLR4 induction of LILRA3 indicated that LPS induces less LILRA3 than ssRNA40 among healthy controls, but not HIV patients. Levels of LILRA3 induction correlated to virus load and CD4 counts in untreated patients. Recombinant LILRA3 can induce a host of proinflammatory genes which include IL-6 and IL-1α, as well as alter the expression of MHC and costimulatory molecules in monocytes and B-cells. CONCLUSION: Our experiments point towards a beneficial role for LILRA3 in virus infections, especially in ssRNA viruses, like HIV, that engage TLR8. However, the potentially beneficial role of LILRA3 is abrogated during a HIV infection. We believe that more work has to be done to study the role of LILRA3 in infectious diseases and that there is a potential for exploring the use of LILRA3 in the treatment of virus infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0248-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4788896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47888962016-03-13 TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads Low, Hui Zhi Ahrenstorf, Gerrit Pommerenke, Claudia Habermann, Nadine Schughart, Klaus Ordóñez, David Stripecke, Renata Wilk, Esther Witte, Torsten Retrovirology Research BACKGROUND: LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection. RESULTS: We analyzed a panel of TLR agonists and found that ssRNA40, a TLR8 agonist, is a potent inducer of LILRA3 in healthy individuals. However, this regulation is much diminished in HIV. Comparison of TLR8 to TLR4 induction of LILRA3 indicated that LPS induces less LILRA3 than ssRNA40 among healthy controls, but not HIV patients. Levels of LILRA3 induction correlated to virus load and CD4 counts in untreated patients. Recombinant LILRA3 can induce a host of proinflammatory genes which include IL-6 and IL-1α, as well as alter the expression of MHC and costimulatory molecules in monocytes and B-cells. CONCLUSION: Our experiments point towards a beneficial role for LILRA3 in virus infections, especially in ssRNA viruses, like HIV, that engage TLR8. However, the potentially beneficial role of LILRA3 is abrogated during a HIV infection. We believe that more work has to be done to study the role of LILRA3 in infectious diseases and that there is a potential for exploring the use of LILRA3 in the treatment of virus infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0248-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-12 /pmc/articles/PMC4788896/ /pubmed/26969150 http://dx.doi.org/10.1186/s12977-016-0248-y Text en © Low et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Low, Hui Zhi Ahrenstorf, Gerrit Pommerenke, Claudia Habermann, Nadine Schughart, Klaus Ordóñez, David Stripecke, Renata Wilk, Esther Witte, Torsten TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads |
title | TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads |
title_full | TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads |
title_fullStr | TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads |
title_full_unstemmed | TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads |
title_short | TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads |
title_sort | tlr8 regulation of lilra3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to cd4 counts and virus loads |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788896/ https://www.ncbi.nlm.nih.gov/pubmed/26969150 http://dx.doi.org/10.1186/s12977-016-0248-y |
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