HIV-Captured DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread

Koh, Wan Hon; López, Paúl; Ajibola, Oluwaseun; Parvarchian, Roshan; Mohammad, Umar; Hnatiuk, Ryan; Kindrachuk, Jason; Murooka, Thomas T.

doi:10.1016/j.isci.2020.101427

Cited by 13 publications

(12 citation statements)

References 123 publications

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“…Increased Langerhans cells have also been shown to associate with HPV clearance ( Shannon et al., 2017 ), and individuals with reduced LC numbers of develop HPV-positive cervical intraepithelial lesions ( Mota et al., 1999 ). However, increased LC numbers may play a role in enhancing HIV susceptibility by binding HIV gp120 and facilitating transmission to CD4 + T cells ( Arrighi et al., 2004 ; Koh et al., 2020 ). Finally, NK cells correlate with HPV clearance ( Prata et al., 2015 ; Bjorkstrom et al., 2021 ), but NK cells were also shown to be biomarkers of increased HIV risk ( Naranbhai et al., 2012 ).…”

Section: Underlying Hpv Infection Increase Hiv Acquisition Riskmentioning

confidence: 99%

HPV and the Risk of HIV Acquisition in Women

Zayats

Murooka

McKinnon

2022

Front. Cell. Infect. Microbiol.

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The risk of HIV acquisition is low on a per-contact basis but increased by transmission co-factors such as other sexually transmitted infections (STIs). Human papillomavirus (HPV) is a prevalent STI that most individuals will acquire HPV in their lifetime. Current HPV vaccines can prevent newly acquired infections, but are largely ineffective against established HPV, complicating worldwide eradication efforts. In addition to being the causative agent of cervical cancer, accumulating evidence suggests that HPV infection and/or accompanying cervical inflammation increase the risk of HIV infection in men and women. The fact that immunological features observed during HPV infection overlap with cellular and molecular pathways known to enhance HIV susceptibility underscore the potential interplay between these two viral infections that fuel their mutual spread. Here we review current insights into how HPV infection and the generation of anti-HPV immunity contribute to higher HIV transmission rates, and the impact of HPV on mucosal inflammation, immune cell trafficking, and epithelial barrier function.

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Section: Underlying Hpv Infection Increase Hiv Acquisition Riskmentioning

confidence: 99%

HPV and the Risk of HIV Acquisition in Women

Zayats

Murooka

McKinnon

2022

Front. Cell. Infect. Microbiol.

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“…As LAs are enriched in rectal tissue (Langman and Rowland, 1986), contain abundant HIV target cells and are known sites of HIV persistence (Chun et al, 2008), rapid access to these structures may facilitate sustained infection and early reservoir formation within the mucosa. Indeed, naïve CD4+ T cells are enriched in LAs (Fenton et al, 2020) and are amenable to both viral transfer and activation by HIV+ DCs, which can promote latency (Cameron et al, 2010) and HIV-susceptible Th17 programs (Koh et al, 2020; Renault et al, 2022; Stieh et al, 2016). Entry into LAs but not LP was also associated with increased SM HIV levels, suggesting LAs as a possible conduit for HIV access to the underlying SM.…”

Section: Discussionmentioning

confidence: 99%

An in situ quantitative map of initial human colorectal HIV transmission

Baharlou

Canete

Vine

et al. 2022

Preprint

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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.Graphical Abstract

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“…Due to exploratory contacts, the virus particles produced from these DCs can be transferred to T cells with high efficiency. In this context, a relatively small amount of DCs containing viral particles can generate an increase in T-cell infection, making it exponential ( 28 , 29 ).The number of interactions established between DCs and TLs, as well as how long they remain in contact, cause T cells differentiation and acquisition of the ability to carry out effector and memory responses. Memory T cells can establish themselves as a reservoir during the chronic phase of viral infection, so that these target cells can cause virus reactivation favoring dissemination ( 30 ).…”

Section: Spread Of Virus In the Immune Systemmentioning

confidence: 99%

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

Espinar-Buitrago

Muñoz‐Fernández

2022

Front. Immunol.

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Due to the success of combined antiretroviral therapy (cART) in recent years, the pathological outcome of Human Immunodeficiency Virus type 1 (HIV-1) infection has improved substantially, achieving undetectable viral loads in most cases. Nevertheless, the presence of a viral reservoir formed by latently infected cells results in patients having to maintain treatment for life. In the absence of effective eradication strategies against HIV-1, research efforts are focused on obtaining a cure. One of these approaches is the creation of therapeutic vaccines. In this sense, the most promising one up to now is based on the establishing of the immunological synapse between dendritic cells (DCs) and T lymphocytes (TL). DCs are one of the first cells of the immune system to encounter HIV-1 by acting as antigen presenting cells, bringing about the interaction between innate and adaptive immune responses mediated by TL. Furthermore, TL are the end effector, and their response capacity is essential in the adaptive elimination of cells infected by pathogens. In this review, we summarize the knowledge of the interaction between DCs with TL, as well as the characterization of the specific T-cell response against HIV-1 infection. The use of nanotechnology in the design and improvement of vaccines based on DCs has been researched and presented here with a special emphasis.

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HIV-Captured DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread

Cited by 13 publications

References 123 publications

HPV and the Risk of HIV Acquisition in Women

HPV and the Risk of HIV Acquisition in Women

An in situ quantitative map of initial human colorectal HIV transmission

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

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