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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number111385
JournalCell Reports
Volume40
Issue number12
DOIs
StatePublished - 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

  • Biochemistry, Genetics and Molecular Biology(all)

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