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Mucosal Responses in the Context of Natural Immunity to HIV

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "HIV Vaccines".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 12399

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Special Issue Editor

Dr. Johanne Poudrier

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Guest Editor

Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
Interests: Mucosal immunity; HIV; BAFF; innate B-cells; dendritic cells

Special Issue Information

Dear Colleagues,

Approximately 37 million people are living with HIV/AIDS worldwide. Most HIV infections are acquired through heterosexual intercourse, and in Africa, nearly 60% of new infections affect women. Currently, there is no cure and the development of vaccines and microbicides remains the best solution to eradicate the pandemic. To this end, the development of effective devices will benefit from studies of individuals who are highly-exposed to HIV and yet remain seronegative (HESN) despite several years of exposure. This special issue aims to further our comprehension of the immune responses that govern mucosal ports of entry in individuals presenting natural immunity to HIV. We therefore encourage the presentation of recent advances in this field. Lessons from vaccination trials and passive immunization studies, and those with non-human primates will also be welcome. Understanding the nature and how immune populations are recruited and maintained within mucosal niche to fight HIV is important to the design of effective preventive/therapeutic approaches.

Dr. Johanne Poudrier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Mucosal responses
natural immunity
HIV
mucosal vaccination
passive immunization

Published Papers (4 papers)

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Research

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15 pages, 4967 KiB

Open AccessArticle

Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs

by Carolina Herrera, Mike D. McRaven, Ken G. Laing, Jayne Dennis, Thomas J. Hope and Robin J. Shattock

Vaccines 2021, 9(3), 231; https://doi.org/10.3390/vaccines9030231 - 08 Mar 2021

Cited by 7 | Viewed by 2019

Abstract

Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure. Full article

(This article belongs to the Special Issue Mucosal Responses in the Context of Natural Immunity to HIV)

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19 pages, 2312 KiB

Open AccessArticle

HIV-Exposed Seronegative Sex Workers Express Low T-Cell Activation and an Intact Ectocervical Tissue Microenvironment

by Maria Röhl, Annelie Tjernlund, Julie Lajoie, Gabriella Edfeldt, Frideborg Bradley, Sofia Bergström, Vilde Kaldhusdal, Alexandra Åhlberg, Anna Månberg, Kenneth Omollo, Geneviève Boily-Larouche, Muhammad Asghar, Douglas S. Kwon, Julius Oyugi, Joshua Kimani, Peter Nilsson, Keith R. Fowke and Kristina Broliden

Vaccines 2021, 9(3), 217; https://doi.org/10.3390/vaccines9030217 - 04 Mar 2021

Cited by 3 | Viewed by 2917

Abstract

Immunological correlates of natural resistance to HIV have been identified in HIV-exposed seronegative (HESN) individuals and include a low-inflammatory genital mucosal status. The cervicovaginal epithelium has not been studied for such correlates despite constituting an important barrier against sexual HIV transmission. To fill this gap in knowledge, we collected samples of blood, cervical mononuclear cells, cervicovaginal lavage, and ectocervical tissue from Kenyan HESN sex workers (n = 29) and controls (n = 33). The samples were analyzed by flow cytometry, protein profiling, 16S rRNA gene sequencing, in situ image analysis, and tissue-based RNA sequencing. A significantly higher relative proportion of regulatory T cells in blood (B7⁺CD25^hiFoxP3⁺CD127^loCD4⁺ and B7⁺Helios⁺FoxP3⁺CD4⁺), and a significantly lower proportion of activated cervical T cells (CCR5⁺CD69⁺CD4⁺ and CCR5⁺CD69⁺CD8⁺), were found in the HESN group compared with the controls. In contrast, there were no statistically significant differences between the study groups in cervicovaginal protein and microbiome compositions, ectocervical epithelial thickness, E-cadherin expression, HIV receptor expression, and tissue RNA transcriptional profiles. The identification of an intact ectocervical microenvironment in HESN individuals add new data to current knowledge about natural resistance to sexual transmission of HIV. Full article

(This article belongs to the Special Issue Mucosal Responses in the Context of Natural Immunity to HIV)

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Graphical abstract

16 pages, 2170 KiB

Open AccessArticle

CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention

by Kanika Vanshylla, Kathrin Held, Tabea M. Eser, Henning Gruell, Franziska Kleipass, Ricarda Stumpf, Kanika Jain, Daniela Weiland, Jan Münch, Berthold Grüttner, Christof Geldmacher and Florian Klein

Vaccines 2021, 9(3), 198; https://doi.org/10.3390/vaccines9030198 - 27 Feb 2021

Cited by 4 | Viewed by 3866

Abstract

Humanized mice are critical for HIV-1 research, but humanized mice generated from cord blood are inefficient at mucosal HIV-1 transmission. Most mucosal HIV-1 transmission studies in mice require fetal tissue-engraftment, the use of which is highly restricted or prohibited. We present a fetal tissue-independent model called CD34T+ with enhanced human leukocyte levels in the blood and improved T cell homing to the gut-associated lymphoid tissue. CD34T+ mice are highly permissive to intra-rectal HIV-1 infection and also show normal env diversification in vivo despite high viral replication. Moreover, mucosal infection in CD34T+ mice can be prevented by infusion of broadly neutralizing antibodies. CD34T+ mice can be rapidly and easily generated using only cord blood cells and do not require any complicated surgical procedures for the humanization process. Therefore, CD34T+ mice provide a novel platform for mucosal HIV-1 transmission studies as well as rapid in vivo testing of novel prevention molecules against HIV-1. Full article

(This article belongs to the Special Issue Mucosal Responses in the Context of Natural Immunity to HIV)

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Review

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22 pages, 529 KiB

Open AccessReview

The Importance of Regulation in Natural Immunity to HIV

by Laurence Blondin-Ladrie, Matheus Aranguren, Kim Doyon-Laliberté, Johanne Poudrier and Michel Roger

Vaccines 2021, 9(3), 271; https://doi.org/10.3390/vaccines9030271 - 18 Mar 2021

Cited by 2 | Viewed by 2990

Abstract

Worldwide, most Human Immunodeficiency Virus (HIV) infections are acquired through heterosexual intercourse, and in sub-Saharan Africa, 59% of new HIV infections affect women. Vaccines and microbicides hold promise for preventing the acquisition of HIV. To this end, the study of HIV highly exposed seronegative (HESN) female commercial sex workers (CSWs), who constitute a model of natural immunity to HIV, provides an exceptional opportunity to determine important clues for the development of preventive strategies. Studies using both female genital tract (FGT) and peripheral blood samples of HESN CSWs, have allowed identifying distinct features, notably low-inflammatory patterns associated with resistance to infection. How this seemingly regulated response is achieved at the initial site of HIV infection remains unknown. One hypothesis is that populations presenting regulatory profiles contribute to the orchestration of potent anti-viral and low-inflammatory responses at the initial site of HIV transmission. Here, we view to update our knowledge regarding this issue. Full article

(This article belongs to the Special Issue Mucosal Responses in the Context of Natural Immunity to HIV)

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