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

Abstract
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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

1. Bhattacharya P
2. Ellegård R
3. Khalid M
4. Svanberg C
5. Govender M
6. Keita Å
7. Söderholm J
8. Myrelid P
9. Shankar E
10. Nyström S
11. Larsson M
(2020) Colorectal mucosa exposed to free and complement opsonized HIV
NCBI Gene Expression Omnibus, GSE149749.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149749

Article and author information

Author details

Pradyot Bhattacharya

Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Rada Ellegård

Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Mohammad Khalid

Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Cecilia Svanberg

Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Melissa Govender

Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Åsa V keita

Dep Biosciences and Clinical Sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Johan D Söderholm

Dep Biosciences and Clinical Sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
Pär Myrelid

Dep Biosciences and Clinical Sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
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.
Sofia Nyström

Department of Biomedical and clinical sciences, Linköping University, Linköping, Sweden

Competing interests
The authors declare that no competing interests exist.
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.

"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

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.