PT  - JOURNAL ARTICLE
AU  - Heeva Baharlou
AU  - Nicolas Canete
AU  - Erica E Vine
AU  - Kevin Hu
AU  - Di Yuan
AU  - Kerrie J Sandgren
AU  - Kirstie M Bertram
AU  - Najla Nasr
AU  - Jake W Rhodes
AU  - Martijn P Gosselink
AU  - Angelina Di Re
AU  - Faizur Reza
AU  - Grahame Ctercteko
AU  - Nimalan Pathma-Nathan
AU  - Geoff Collins
AU  - James Toh
AU  - Ellis Patrick
AU  - Muzlifah A Haniffa
AU  - Jacob D. Estes
AU  - Scott N Byrne
AU  - Anthony L Cunningham
AU  - Andrew N Harman
TI  - An <em>in situ</em> quantitative map of initial human colorectal HIV transmission
AID  - 10.1101/2022.04.30.490175
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.04.30.490175
4099  - http://biorxiv.org/content/early/2022/05/01/2022.04.30.490175.short
4100  - http://biorxiv.org/content/early/2022/05/01/2022.04.30.490175.full
AB  - The initial immune response to HIV is critical in determining transmission. However, due to technical limitations we still do not have a comparative map of early mucosal transmission events. We combined RNAscope, cyclic-immunofluorescence and novel image analysis tools to quantify HIV transmission dynamics in intact human colorectal tissue. We mapped HIV enrichment to mucosal dendritic cells (DC) and submucosal macrophages, but not CD4+ T-cells, the primary targets of downstream infection. DCs appeared to funnel virus to lymphoid aggregates which acted as early sanctuaries of high viral titres whilst facilitating HIV passage to the submucosa. Finally, HIV entry induced rapid 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 maximise the likelihood of mucosal infection, and provide a framework for in situ studies of host pathogen interactions and immune mediated pathologies.Highlights- in situ quantification of host cellular microenvironment response to pathogen invasion in human colorectal tissue.- HIV first localises to mucosal DCs and submucosal macrophages, but not CD4+ T cells.- Viral enrichment first occurs in lymphoid aggregates which is associated with passage into the submucosa.- Early localisation of HIV to CD4+ T cells is associated with interactions with DCs and macrophages.Competing Interest StatementThe authors have declared no competing interest.