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

Abstract

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 24h revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96h in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, i.e. Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, e.g. 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.

Data availability

Sequencing data (RNA seq) have been deposited in GEO, under the accession number GSE149749.

The following data sets were generated

Article and author information

Author details

  1. Pradyot Bhattacharya

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Rada Ellegård

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Mohammad Khalid

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Cecilia Svanberg

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Melissa Govender

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Åsa V keita

    Dep Biosciences and Clinical Sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Johan D Söderholm

    Dep Biosciences and Clinical Sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Pär Myrelid

    Dep Biosciences and Clinical Sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  9. Esaki M Shankar

    Dept. of Life Sciences, Central University of Tamil Nadu Neelakudi, Thiruvarur, India
    Competing interests
    The authors declare that no competing interests exist.
  10. Sofia Nyström

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  11. Marie Larsson

    Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden
    For correspondence
    marie.larsson@liu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4524-0177

Funding

Vetenskapsrådet (Project grant)

  • Marie Larsson

Läkare emot AIDS (Project grant)

  • Marie Larsson

Forsknings-ALF (Project grant)

  • Marie Larsson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was approved by the Linköping University Ethical Review Board (Ethical permit EPN M206-06). The subjects were informed about the study at the clinic and verbal consents were obtained and documented from all participating subjects, as approved by the Linköping University Ethical Review Board. The study included both male and female adult subjects who were 18 years or older.

Copyright

© 2020, Bhattacharya et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Pradyot Bhattacharya
  2. Rada Ellegård
  3. Mohammad Khalid
  4. Cecilia Svanberg
  5. Melissa Govender
  6. Åsa V keita
  7. Johan D Söderholm
  8. Pär Myrelid
  9. Esaki M Shankar
  10. Sofia Nyström
  11. Marie Larsson
(2020)
Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
eLife 9:e57869.
https://doi.org/10.7554/eLife.57869

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https://doi.org/10.7554/eLife.57869