Transepithelial transport of HIV-1 by M cells is receptor-mediated

Fotopoulos, Grigorios; Harari, Alexandre; Michetti, Pierre; Trono, Didier; Pantaleo, Giuseppe; Kraehenbuhl, Jean–Pierre

doi:10.1073/pnas.142586899

Cited by 96 publications

(65 citation statements)

References 31 publications

(30 reference statements)

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“…Mechanisms of uptake and transport were studied by microscopy and by pharmacological inhibition studies in human FAE tissue, as well as in the in vitro lymphocyte-epithelial cell coculture model of human FAE initially described by Kerneís et al, 11 and subsequently used by several groups to study FAE and M-cell function. [12][13][14][15][16][17][18] Our findings show that human ileal FAE is not only structurally, but also functionally distinct from regular VE, with enhanced transport of antigens and bacteria into the underlying lymphoid tissue.…”

mentioning

confidence: 64%

“…In a paper by Kerneís et al 11 it was shown that coculture of Peyer's patch lymphocytes and intestinal epithelial cells may trigger conversion of the epithelial cells to M cells. This model and variants of it have been used to study M-cell function, [12][13][14][15][16][17] and by using our previously established modification 18 of the original model, mechanisms of antigen and bacterial uptake could be studied. Briefly, intestinal epithelial Caco-2 cells were grown on Matrigelt (Becton Dickinson, USA) coated polycarbonate filters (Costar, Baedvenhorp, NL, USA) with a mean pore size of 3.0 mm.…”

Section: Coculture Modelmentioning

confidence: 99%

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Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum

Keita¹,

Gullberg

Ericson

et al. 2006

Laboratory Investigation

100

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The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51 Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal-and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51 Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial-epithelial cell interactions and delivery of antigens to the mucosal immune system.

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mentioning

confidence: 64%

Section: Coculture Modelmentioning

confidence: 99%

Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum

Keita¹,

Gullberg

Ericson

et al. 2006

Laboratory Investigation

100

View full text Add to dashboard Cite

show abstract

“…Although there is no direct evidence that LCs are the initial cells infected with HIV in humans, genetic data generated in large cohorts make it clear that CCR5 genotype is a major determinant for initial HIV susceptibility (16)(17)(18)(19). Whether CCR5 influences initial infection at the level of the LCs, at the level of the epithelial cell (43,44), at early replication steps in lymphoid tissue, or at multiple sites, however, is less clear. The former theories can be described as primary gatekeeper models, whereas the latter process represents a viral fitness model (40).…”

Section: Discussionmentioning

confidence: 99%

R5 HIV productively infects Langerhans cells, and infection levels are regulated by compoundCCR5polymorphisms

Kawamura

Gulden

Sugaya

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

177

165

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Langerhans cells (LCs) are suspected to be initial targets for HIV after sexual exposure (by becoming infected or by capturing virus). Here, productive R5 HIV infection of LC ex vivo and LC-mediated transmission of virus to CD4 ؉ T cells were both found to depend on CCR5. By contrast, infection of monocyte-derived dendritic cells and transfer of infection from monocyte-derived dendritic cells to CD4 ؉ T cells were mediated by CCR5-dependent as well as DCspecific ICAM-3-grabbing nonintegrin-dependent pathways. Furthermore, in 62 healthy individuals, R5 HIV infection levels in LCs ex vivo were associated with CCR5 genotype. Specifically, genotyping for ORF⌬32 revealed that LCs isolated from ORF⌬32͞wt individuals were significantly less susceptible to HIV when compared with LCs isolated from ORFwt͞wt individuals (P ‫؍‬ 0.016). Strikingly, further genetic analyses of the A-2459G CCR5 promoter polymorphism in ORF⌬32͞wt heterozygous individuals revealed that LCs isolated from ؊2459A͞G ϩ ORF⌬32͞wt individuals were markedly less susceptible to HIV than were LCs from ؊2459A͞A ϩ ORF⌬32͞wt individuals (P ‫؍‬ 0.012). Interestingly, these genetic susceptibility data in LCs parallel those of genetic susceptibility studies performed in cohorts of HIV-infected individuals. Thus, we suggest that CCR5-mediated infection of LCs, and not capture of virus by LCs, provides a biologic basis for understanding certain aspects of host genetic susceptibility to initial HIV infection.

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“…For example, poliovirus translocates from the apical to the basolateral compartment in a temperaturedependent manner when polarized Caco-2 cell monolayers are cocultured with Peyer's patch lymphocytes to induce M-like cells (34). Another study demonstrated that a human immunodeficiency virus type 1 (HIV-1) strain tropic for the chemokine receptor CXCR4 (but not for CCR5) infects and is transported across polarized Caco-2 monolayers cocultured with B cells in a receptor-dependent manner (35). In addition, human T cell leukemia virus type 1 (HTLV-1) crosses polarized Caco-2 cell monolayers without disruption of tight junctions or infection of the epithelium to productively infect dendritic cells in the basolateral compartment (36).…”

mentioning

confidence: 99%

Murine Norovirus Transcytosis across anIn VitroPolarized Murine Intestinal Epithelial Monolayer Is Mediated by M-Like Cells

Gonzalez-Hernandez

Liu

Blanco

et al. 2013

J Virol

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Transepithelial transport of HIV-1 by M cells is receptor-mediated

Cited by 96 publications

References 31 publications

Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum

Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum

R5 HIV productively infects Langerhans cells, and infection levels are regulated by compoundCCR5polymorphisms

Murine Norovirus Transcytosis across anIn VitroPolarized Murine Intestinal Epithelial Monolayer Is Mediated by M-Like Cells

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