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

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. ByrneAnthony L. Cunningham, Andrew N. Harman

Vaccine and Gene Therapy Institute

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English (US)
Article number	111385
Journal	Cell Reports
Volume	40
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2022.111385
State	Published - Sep 20 2022

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2022.111385

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Baharlou, H., Canete, N., Vine, E. E., Hu, K., Yuan, D., Sandgren, K. J., Bertram, K. M., Nasr, N., Rhodes, J. W., Gosselink, M. P., Di Re, A., Reza, F., Ctercteko, G., Pathma-Nathan, N., Collins, G., Toh, J., Patrick, E., Haniffa, M. A., Estes, J. D., ... Harman, A. N. (2022). An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission. Cell Reports, 40(12), Article 111385. https://doi.org/10.1016/j.celrep.2022.111385

Baharlou, H, Canete, N, Vine, EE, Hu, K, Yuan, D, Sandgren, KJ, Bertram, KM, Nasr, N, Rhodes, JW, Gosselink, MP, Di Re, A, Reza, F, Ctercteko, G, Pathma-Nathan, N, Collins, G, Toh, J, Patrick, E, Haniffa, MA, Estes, JD, Byrne, SN, Cunningham, AL & Harman, AN 2022, 'An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission', Cell Reports, vol. 40, no. 12, 111385. https://doi.org/10.1016/j.celrep.2022.111385

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

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",

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

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year = "2022",

month = sep,

day = "20",

doi = "10.1016/j.celrep.2022.111385",

language = "English (US)",

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T1 - An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission

AU - Baharlou, Heeva

AU - Canete, Nicolas

AU - Vine, Erica E.

AU - Hu, Kevin

AU - Yuan, Di

AU - Sandgren, Kerrie J.

AU - Bertram, Kirstie M.

AU - Nasr, Najla

AU - Rhodes, Jake W.

AU - Gosselink, Martijn P.

AU - Di Re, Angelina

AU - Reza, Faizur

AU - Ctercteko, Grahame

AU - Pathma-Nathan, Nimalan

AU - Collins, Geoff

AU - Toh, James

AU - Patrick, Ellis

AU - Haniffa, Muzlifah A.

AU - Estes, Jacob D.

AU - Byrne, Scott N.

AU - Cunningham, Anthony L.

AU - Harman, Andrew N.

PY - 2022/9/20

Y1 - 2022/9/20

N2 - 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.

AB - 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.

KW - CP: Immunology

KW - CP: Microbiology

KW - HIV explant infection

KW - RNAScope

KW - cell-cell viral transfer

KW - cyclic immunofluorescence

KW - dendritic cell

KW - in situ imaging

KW - isolated lymphoid follicle

KW - lymphoid aggregate

KW - mucosal HIV transmission

KW - mucosal immunology

KW - neighborhood analysis

KW - systems biology

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AN - SCOPUS:85138129640

SN - 2211-1247

VL - 40

JO - Cell Reports

JF - Cell Reports

IS - 12

M1 - 111385

ER -

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

Abstract

Keywords

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