HIV transmission from infected CD4+ T cells to allogenic T and dendritic cells is inhibited by broadly neutralizing antibodies

Ducloy, Camille; Su, Bin; Mayr, Luzia; Klingler, Jéromine; Decoville, Thomas; Schmidt, Sylvie; Laumond, Géraldine; Salomé, Nathalie; Bahram, Seiamak; Moog, Christiane

doi:10.1097/qad.0000000000001834

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…Thus, it will be important to ascertain if a higher bn-mAb concentration will be necessary to prevent rectal transmission. Although the addition of seminal proteins did not impact VRC01 neutralization against cell-free Bal26 in the rectal explant challenge, further work will extend previous reports to address the role of seminal proteins in the neutralization of other viruses at mucosal sites (18), as well as the role of other antibodies in the prevention of infection from cell-associated viruses in semen (74,75).…”

Section: Discussionmentioning

confidence: 74%

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge

Astronomo¹,

Lemos²,

Narpala³

et al. 2021

Journal of Clinical Investigation

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Allergy and Infectious Diseases (NIAID), the HVTN 104 study sponsor and originator of the VRC01 antibody used in the study. All other authors are recipients of NIAID funding paid to their institutions, and this publication is a result of activities funded by the NIAID. AM, JL, MP and SN are not involved with the process of funding these awards nor in their administration of scientific aspects and, in accordance with NIAID policies, are deferred from decisions regarding funding of coauthors for a requisite period. No other authors declare potential conflicts of interest. Role of the funder:The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Section: Discussionmentioning

confidence: 74%

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge

Astronomo¹,

Lemos²,

Narpala³

et al. 2021

Journal of Clinical Investigation

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“…Overall, our findings showed that HSP plays a pivotal role in recruiting CD11c+ MNPs at the apical side of the colonic epithelium and, when infected, serves as a vector for the virus to get in close contact with the colonic mucosa and relevant cells. Cavarelli and Baharlou, with two different techniques, highlighted how free HIV initially infects dendritic cells ( 14 , 43 ), and postulated that these cells are responsible for the subsequent viral spread to surrounding CD4+ T cells in the intestinal mucosa ( 44 , 45 ). In sexual transmission virions, however, are carried by semen and seminal fluid, and are rarely found in free form adjacent to colonic epithelial tissue.…”

Section: Discussionmentioning

confidence: 99%

Human seminal plasma stimulates the migration of CD11c+ mononuclear phagocytes to the apical side of the colonic epithelium without altering the junctional complexes in an ex vivo human intestinal model

et al. 2023

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IntroductionHuman immunodeficiency virus type 1 (HIV) transmission mostly occurs through the genital and intestinal mucosae. Although HIV-1 transmission has been extensively investigated, gaps remain in understanding the initial steps of HIV entry through the colonic mucosa. We previously showed that HIV can selectively trigger mononuclear phagocytes (MNP) to migrate within colonic epithelial cells to sample virions. Mucosal exposure to human seminal plasma (HSP), rich in pro- and anti-inflammatory cytokines, chemokines and growth factors, may as well induce alterations of the colonic mucosa and recruit immune cells, hence, affecting pathogen sampling and transmission.MethodsHere, we studied the role of HSP on the paracellular intestinal permeability by analyzing the distribution of two proteins known to play a key role in controlling the intestinal barrier integrity, namely the tight junctions-associated junctional adhesion molecule (JAM-A) and the adherents junction associated protein E-cadherin (E-CAD), by immunofluorescence and confocal microscopy. Also, we evaluated if HSP promotes the recruitment of MNP cells, specifically, the CD11c and CD64 positive MNPs, to the apical side of the human colonic mucosa. At this scope, HSP of HIV-infected and uninfected individuals with known fertility status was tested for cytokines, chemokines and growth factors concentration and used in an ex vivo polarized colonic tissue culture system to mimic as closely as possible the physiological process.ResultsHSP showed statistically significant differences in cytokines and chemokines concentrations between the three groups of donors, i.e. HIV infected, or uninfected fertile or randomly identified. Nevertheless, we showed that in the ex vivo tissue culture HSP in general, neither affected the morphological structure of the colonic mucosa nor modulated the paracellular intestinal permeability. Interestingly, CD11c+ MNP cells migrated to the apical surface of the colonic epithelium regardless, if incubated with HIV-infected or -uninfected HSPs, while CD64+ MNP cells, did not change their distribution within the colonic mucosa.DiscussionIn conclusion, even if HSP did not perturb the integrity of the human colonic mucosa, it affected the migration of a specific subset of MNPs that express CD11c towards the apical side of the colonic mucosa, which in turn may be involved in pathogen sampling.

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HIV transmission from infected CD4+ T cells to allogenic T and dendritic cells is inhibited by broadly neutralizing antibodies

Cited by 2 publications

References 46 publications

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge

Human seminal plasma stimulates the migration of CD11c+ mononuclear phagocytes to the apical side of the colonic epithelium without altering the junctional complexes in an ex vivo human intestinal model

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