An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission

Heeva Baharlou; Nicolas Canete; Erica E Vine; Kevin Hu; Di Yuan; Kerrie J Sandgren; Kirstie M Bertram; Najla Nasr; Jake W Rhodes; Martijn P Gosselink; Angelina Di Re; Faizur Reza; Grahame Ctercteko; Nimalan Pathma-Nathan; Geoff Collins; James Toh; Ellis Patrick; Muzlifah A Haniffa; Jacob D Estes; Scott N Byrne; Anthony L Cunningham; Andrew N Harman

doi:10.1016/j.celrep.2022.111385

An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission

Cell Rep. 2022 Sep 20;40(12):111385. doi: 10.1016/j.celrep.2022.111385.

Authors

Heeva Baharlou¹, Nicolas Canete², Erica E Vine², Kevin Hu², Di Yuan², Kerrie J Sandgren², Kirstie M Bertram², Najla Nasr², Jake W Rhodes², Martijn P Gosselink³, Angelina Di Re³, Faizur Reza³, Grahame Ctercteko³, Nimalan Pathma-Nathan³, Geoff Collins³, James Toh³, Ellis Patrick⁴, Muzlifah A Haniffa⁵, Jacob D Estes⁶, Scott N Byrne², Anthony L Cunningham², Andrew N Harman⁷

Affiliations

¹ Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health Sydney, Sydney, NSW, Australia. Electronic address: [email protected].
² Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health Sydney, Sydney, NSW, Australia.
³ Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; Department of Colorectal Surgery, Westmead Hospital, Westmead, NSW 2145, Australia.
⁴ Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; The University of Sydney, School of Maths and Statistics, Faculty of Science, Sydney, NSW, Australia.
⁵ Biosciences Institute, The University of Newcastle, Newcastle upon Tyne, UK; Wellcome Sanger Institute, Hinxton, UK; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁶ Vaccine & Gene Therapy Institute, Oregon Health & Science University, Portland, OR, USA; Division of Pathobiology & Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA.
⁷ Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia; The University of Sydney, School of Medical Sciences, Faculty of Medicine and Health Sydney, Sydney, NSW, Australia. Electronic address: [email protected].

PMID: 36130503
DOI: 10.1016/j.celrep.2022.111385

Abstract

The initial immune response to HIV determines transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. By combining RNAscope, cyclic immunofluorescence, and image analysis tools, we quantify HIV transmission signatures in intact human colorectal explants within 2 h of topical exposure. We map HIV enrichment to mucosal dendritic cells (DCs) and submucosal macrophages, but not CD4⁺ T cells, the primary targets of downstream infection. HIV⁺ DCs accumulate near and within lymphoid aggregates, which act as early sanctuaries of high viral titers while facilitating HIV passage to the submucosa. Finally, HIV entry induces recruitment and clustering of target cells, facilitating DC- and macrophage-mediated HIV transfer and enhanced infection of CD4⁺ T cells. These data demonstrate a rapid response to HIV structured to maximize the likelihood of mucosal infection and provide a framework for in situ studies of host-pathogen interactions and immune-mediated pathologies.

Keywords: CP: Immunology; CP: Microbiology; HIV explant infection; RNAScope; cell-cell viral transfer; cyclic immunofluorescence; dendritic cell; in situ imaging; isolated lymphoid follicle; lymphoid aggregate; mucosal HIV transmission; mucosal immunology; neighborhood analysis; systems biology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes
Colorectal Neoplasms* / pathology
Dendritic Cells
HIV Infections*
HIV-1*
Host-Pathogen Interactions
Humans