Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells

HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal...

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Main Authors: Pradyot Bhattacharya, Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Melissa Govender, Åsa V Keita, Johan D Söderholm, Pär Myrelid, Esaki M Shankar, Sofia Nyström, Marie Larsson
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Language:English
Published: eLife Sciences Publications Ltd 2020-09-01
Series:eLife
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Online Access:https://elifesciences.org/articles/57869
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author Pradyot Bhattacharya
Rada Ellegård
Mohammad Khalid
Cecilia Svanberg
Melissa Govender
Åsa V Keita
Johan D Söderholm
Pär Myrelid
Esaki M Shankar
Sofia Nyström
Marie Larsson
author_facet Pradyot Bhattacharya
Rada Ellegård
Mohammad Khalid
Cecilia Svanberg
Melissa Govender
Åsa V Keita
Johan D Söderholm
Pär Myrelid
Esaki M Shankar
Sofia Nyström
Marie Larsson
author_sort Pradyot Bhattacharya
collection DOAJ
description HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.
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spelling doaj.art-5784e462455c4401acbb84dc90a711e02022-12-22T04:29:18ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.57869Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cellsPradyot Bhattacharya0Rada Ellegård1Mohammad Khalid2Cecilia Svanberg3Melissa Govender4Åsa V Keita5Johan D Söderholm6Pär Myrelid7Esaki M Shankar8Sofia Nyström9Marie Larsson10https://orcid.org/0000-0002-4524-0177Division of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Surgery, Orthopedics and Oncology, Linköping University, Linköping, SwedenDivision of Surgery, Orthopedics and Oncology, Linköping University, Linköping, SwedenDivision of Surgery, Orthopedics and Oncology, Linköping University, Linköping, SwedenCenter of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia; Division of Infection Biology and Medical Microbiology, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, IndiaDivision of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenDivision of Molecular Medicine and Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenHIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.https://elifesciences.org/articles/57869HIVcolorectal mucosavirus infectiont lymphocytesinnnate responses
spellingShingle Pradyot Bhattacharya
Rada Ellegård
Mohammad Khalid
Cecilia Svanberg
Melissa Govender
Åsa V Keita
Johan D Söderholm
Pär Myrelid
Esaki M Shankar
Sofia Nyström
Marie Larsson
Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
eLife
HIV
colorectal mucosa
virus infection
t lymphocytes
innnate responses
title Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
title_full Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
title_fullStr Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
title_full_unstemmed Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
title_short Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
title_sort complement opsonization of hiv affects primary infection of human colorectal mucosa and subsequent activation of t cells
topic HIV
colorectal mucosa
virus infection
t lymphocytes
innnate responses
url https://elifesciences.org/articles/57869
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