CD32CD4 memory T cells are enriched for total HIV-1 DNA in tissues from humanized mice.

CD32 has raised conflicting results as a putative marker of the HIV-1 reservoir. We measured CD32 expression in tissues from viremic and virally suppressed humanized mice treated relatively early or late after HIV-1 infection with combined antiretroviral therapy. CD32 was expressed in a small fraction of the memory CD4 T-cell subsets from different tissues in viremic and aviremic mice, regardless of treatment initiation time.

Development of Mimokines, chemokine N terminus-based CXCR4 inhibitors optimized by phage display and rational design.

The chemokine receptor CXCR4 (C-X-C chemokine receptor type 4 also known as fusin or CD184 (cluster of differentiation 184)) is implicated in various biological and pathological processes of the hematopoietic and immune systems. CXCR4 is also one of the major coreceptors for HIV-1 entry into target cells and is overexpressed in many cancers, supporting cell survival, proliferation, and migration. CXCR4 is thus an extremely relevant drug target.

Human CD56CD16 Cells As an Individualized Natural Killer Cell Subset.

Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of the relative expression of the adhesion molecule CD56 and the activating receptor CD16. Whereas blood CD56CD16 NK cells are classically viewed as immature precursors and cytokine producers, the larger CD56CD16 subset is considered as the most cytotoxic one. In peripheral blood of healthy donors, we noticed the existence of a population of CD56CD16 NK cells that was frequently higher in number than the CD56 subsets and even expanded in occasional control donors but also in transporter associated with antigen processing-deficient patients, two familial hemophagocytic lymphohistiocytosis type II patients, and several common variable immunodeficiency patients.

Dysfunctions in the migratory phenotype and properties of circulating immature transitional B cells during HIV-1 infection.

Objective: The frequency of immature transitional B cells is increased in blood of HIV-1-infected individuals. We investigated whether HIV-1 infection affects expression and function of chemokine receptors important for egress of immature transitional B cells from bone marrow and migration to lymphoid organs.

Design: This is a cross-sectional study analysing the migratory phenotype and function of immature transitional B cells in HIV-1-infected individuals, in relation to antiretroviral treatment and age.

Increased extrafollicular expression of the B-cell stimulatory molecule CD70 in HIV-1-infected individuals.

Objective: CD70 molecules expressed by activated T cells provide potent B cell stimulatory signals. We hypothesized that an altered CD70 expression might contribute to B cell abnormalities during HIV-1 infection.

Design: CD70 expression and the functional and migratory properties of the CD4CD70 T lymphocytes were analyzed in HIV-1-infected patients and in humanized mice.

Neutralising properties of peptides derived from CXCR4 extracellular loops towards CXCL12 binding and HIV-1 infection.

The chemokine receptor CXCR4 interacts with a single endogenous chemokine, CXCL12, and regulates a wide variety of physiological and pathological processes including inflammation and metastasis development. CXCR4 also binds the HIV-1 envelope glycoprotein, gp120, resulting in viral entry into host cells. Therefore, CXCR4 and its ligands represent valuable drug targets.

Development of PLGA-mannosamine nanoparticles as oral protein carriers.

Here we report the development of polymeric nanoparticles, made of poly(lactide-co-glycolide) (PLGA) chemically modified with mannosamine (MN), intended to specifically interact with the intestinal mucosa and facilitate the intestinal transport of proteins. PLGA-MN nanoparticles displayed nanometric size and a negative zeta potential, which was lower than that of the PLGA nanoparticles. This correlate well with the preferential location of the MN group on the nanoparticles surface obtained by X-ray photoelectron spectroscope (XPS).

Function, diversity and therapeutic potential of the N-terminal domain of human chemokine receptors.

Chemokines and their receptors play fundamental roles in many physiological and pathological processes such as leukocyte trafficking, inflammation, cancer and HIV-1 infection. Chemokine-receptor interactions are particularly intricate and therefore require precise orchestration. The flexible N-terminal domain of human chemokine receptors has regularly been demonstrated to hold a crucial role in the initial recognition and selective binding of the receptor ligands.

Engineering and screening the N-terminus of chemokines for drug discovery.

Chemokines are small chemoattractive proteins involved in many important physiological and pathological processes such as leukocyte mobilisation, inflammation, cancer and HIV-1 infection. The N-terminus of chemokines was shown to be crucial for interaction and activation with their cognate receptors. Therefore, multiple strategies including elongation, truncation, mutagenesis or chemical modifications of chemokine N-terminus were developed to identify analogues with modified selectivity displaying antagonist or enhanced agonist activities.

Acylated and unacylated ghrelin binding to membranes and to ghrelin receptor: towards a better understanding of the underlying mechanisms.

The O-octanoylation of human ghrelin is a natural post-translational modification that enhances its binding to model membranes and could potentially play a central role in ghrelin biological activities. Here, we aimed to clarify the mechanisms that drive ghrelin to the membrane and hence to its receptor that mediates most of its endocrinological effects. As the acylation enhances ghrelin lipophilicity and that ghrelin contains many basic residues, we examined the electrostatic attraction and/or hydrophobic interactions with membranes.

Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination.

The presence of RGD on nanoparticles allows the targeting of beta1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in PLGA-based nanoparticles. RGD and RGDp significantly increased the transport of nanoparticles across an in vitro model of human M cells as compared to enterocytes.

PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination.

To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called "photografting" which covalently linked RGD peptides mainly on the PEG moiety of the PCL-PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed.

Helodermin-loaded nanoparticles: characterization and transport across an in vitro model of the follicle-associated epithelium.

M cells represent a potential portal for oral delivery of peptides and proteins due to their high endocytosis abilities. An in vitro model of human FAE (co-cultures) was used to evaluate the influence of M cells on the transport of free and encapsulated helodermin--a model peptide--across the intestinal epithelium. M cells enhanced transport of intact helodermin (18-fold, Papp=3 x 10(-6) cm s(-1)).

An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells.

An alternative in vitro model of human follicle-associated epithelium (FAE) to study nanoparticle transport mechanisms by M cells was developed and characterized. The previous in vitro model of human FAE has been improved by inverting inserts after Caco-2 cell seeding. Raji and M cells were identified only in inverted co-culture cell monolayers by immunohistochemistry, confocal microscopy, and electron microscopy.

Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach.

Peptides and proteins remain poorly bioavailable upon oral administration. One of the most promising strategies to improve their oral delivery relies on their association with colloidal carriers, e.g.