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Lymph Node Innate Lymphoid Cells (ILCs) in HIV Infected Children are Highly Activated Despite Sustained Depletion in Blood

46 Pages Posted: 20 Aug 2019 Sneak Peek Status: Under Review

See all articles by Alveera Singh

Alveera Singh

Africa Health Research Institute

Julia Roider

Africa Health Research Institute

Samuel Kazer

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

Kami Krista

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

Jane Millar

University of Oxford - Department of Paediatrics

Osaretin Emmanuel Asowata

Africa Health Research Institute

Abigail Ngoepe

Africa Health Research Institute

Duran Ramsuran

Africa Health Research Institute

Rabiah Fardoos

Africa Health Research Institute

Amanda Ardain

Africa Health Research Institute

Maximilian Muenchhoff

University of Oxford - Department of Paediatrics

Warren Kuhn

University of KwaZulu-Natal - ENT Department

Farina Karim

Africa Health Research Institute

Thumbi N'dungu

University of KwaZulu-Natal - HIV Pathogenesis Programme

Alex Shalek

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

Philip Goulder

University of Oxford - Department of Paediatrics

Alasdair Leslie

Africa Health Research Institute

Henrik Kloverpris

Africa Health Research Institute

More...

Abstract

Innate lymphoid cells (ILCs) are important for response to infection and immune development in early life. HIV infection in adults has a profound effect on ILCs, but the impact from birth is unknown. Here we studied vertically HIV infected children from birth, and found severe and persistent depletion of all circulating ILCs. In contrast to CD4 T-cells, circulating ILCs are not restored by long-term antiretroviral therapy, but could be rescued by treatment from birth. Remaining helper ILCs in blood were transcriptionally silent, whilst NK cells display limited regulation of genes associated with functional impairment, and CD4 T-cells show strong transcriptional activity. In stark contrast to blood, lymphoid (tonsil) tissue ILCs from infected children had a robust and coordinated transcriptional response to infection, while CD4 T-cell subsets were transcriptionally silent. These data suggest an important and on-going role for ILCs in lymphoid tissue of HIV infected children that requires further investigation.

Keywords: Innate Lymphoid Cells (ILCs), Paediatric HIV infection, Paediatric Slow Progression, ILCs in paediatric HIV infected lymphoid tissue, Transcriptional profiling of lymphoid tissue ILCs (RNAseq)

Suggested Citation

Singh, Alveera and Roider, Julia and Kazer, Samuel and Krista, Kami and Millar, Jane and Asowata, Osaretin Emmanuel and Ngoepe, Abigail and Ramsuran, Duran and Fardoos, Rabiah and Ardain, Amanda and Muenchhoff, Maximilian and Kuhn, Warren and Karim, Farina and N'dungu, Thumbi and Shalek, Alex and Goulder, Philip and Leslie, Alasdair and Kloverpris, Henrik, Lymph Node Innate Lymphoid Cells (ILCs) in HIV Infected Children are Highly Activated Despite Sustained Depletion in Blood (August 20, 2019). CELL-REPORTS-D-19-03089. Available at SSRN: https://ssrn.com/abstract=3439665 or http://dx.doi.org/10.2139/ssrn.3439665
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Alveera Singh

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Julia Roider

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Samuel Kazer

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Kami Krista

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Jane Millar

University of Oxford - Department of Paediatrics

United Kingdom

Osaretin Emmanuel Asowata

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Abigail Ngoepe

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Duran Ramsuran

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Rabiah Fardoos

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Amanda Ardain

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Maximilian Muenchhoff

University of Oxford - Department of Paediatrics

United Kingdom

Warren Kuhn

University of KwaZulu-Natal - ENT Department

South Africa

Farina Karim

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Thumbi N'dungu

University of KwaZulu-Natal - HIV Pathogenesis Programme

South Africa

Alex Shalek

Massachusetts Institute of Technology (MIT) - David H. Koch Institute for Integrative Cancer Research

77 Massachusetts Avenue
50 Memorial Drive
Cambridge, MA 02139-4307
United States

Philip Goulder

University of Oxford - Department of Paediatrics

United Kingdom

Alasdair Leslie

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Henrik Kloverpris (Contact Author)

Africa Health Research Institute

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, 4001
South Africa

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