Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Infection.

Understanding macrophage behavior is key to decipher (Mtb) pathogenesis. We studied the phenotype and ability of human monocyte-derived cells polarized with active vitamin D [1,25(OH)D] to control intracellular Mtb infection compared with polarization of conventional subsets, classical M1 or alternative M2. Human blood-derived monocytes were treated with active vitamin D or different cytokines to obtain 1,25(OH)D-polarized as well as M1- and M2-like cells or fully polarized M1 and M2 subsets.

Evaluation of the immunogenic capability of the BCG strains BCGΔBCG1419c and BCGΔBCG1416c in a three-dimensional human lung tissue model.

Tuberculosis (TB) still remains as an unmet global threat. The current vaccine is not fully effective and novel alternatives are needed. Here, two vaccine candidate strains derived from BCG carrying deletions in the BCG1416c or BCG1419c genes were analysed for their capacity to modulate the cytokine/chemokine profile and granuloma formation in a human lung tissue model (LTM).

Inhibition of Tissue Matrix Metalloproteinases Interferes with -Induced Granuloma Formation and Reduces Bacterial Load in a Human Lung Tissue Model.

Granulomas are hallmarks of pulmonary tuberculosis (TB) and traditionally viewed as host-protective structures. However, recent evidence suggest that (Mtb) uses its virulence factors to stimulate the formation of granuloma. In the present study, we investigated the contribution of matrix metalloproteinases (MMPs), host enzymes that cause degradation of the extracellular matrix, to granuloma formation and bacterial load in Mtb-infected tissue.

Enhanced CD8 cytolytic T cell responses in the peripheral circulation of patients with sarcoidosis and non-Löfgren's disease.

Background: The role of CD4 T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8 cytolytic T cells (CTLs).

Methods: CD8 CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8 T cells, using flow cytometry.

Anti-mycobacterial activity correlates with altered DNA methylation pattern in immune cells from BCG-vaccinated subjects.

The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection.

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M.

Interleukins 15 and 12 in combination expand the selective loss of natural killer T cells in HIV infection in vitro.

The present study evaluated the frequency and receptor expression pattern of invariant natural killer T (iNKT) cells in human immunodeficiency virus (HIV)-infected individuals. Further, the effect of IL-15 + IL-12 stimulation on iNKT cells was also assessed. The study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals, and patients with HIV and tuberculosis coinfection (HIV-TB).

Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue.

The widely used animal models for tuberculosis (TB) display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model.

Effect of recombinant cytokines on the expression of natural killer cell receptors from patients with TB or/and HIV infection.

Background: NK cells express several specialized receptors through which they recognize and discriminate virally-infected/tumor cells efficiently from healthy cells and kill them. This ability to lyse is regulated by an array of inhibitory or activating receptors. The present study investigated the frequency of various NK receptors expressed by NK cell subsets from HIV-infected TB patients.