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Host Macrophages (host + macrophage)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Lysosomal ubiquitin and the demise of Mycobacterium tuberculosis

CELLULAR MICROBIOLOGY, Issue 12 2007
Georgiana E. Purdy
Summary The antimicrobial activity of macrophages is mediated by both oxidative and non-oxidative mechanisms. Oxidative mechanisms include the action of reactive oxygen and nitrogen intermediates on bacteria. Non-oxidative mechanisms include the maturation of the phagosome into an acidified, hydrolytically active compartment as well as the action of antimicrobial peptides. Mycobacterium tuberculosis parasitizes the host macrophage by arresting the normal maturation of its phagosome and resides in a compartment that fails to fuse with lysosomes. When bacteria are unable to regulate phagosome maturation, such as in activated macrophages, they are delivered to lysosomal compartments, where they are killed. Recent data indicate that the antimycobacterial mechanism of the lysosome is due in part to the action of ubiquitin-derived peptides. [source]

Mitogen-activated protein kinases regulate Mycobacterium avium -induced tumor necrosis factor-, release from macrophages

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2002
Asima Bhattacharyya
Abstract Tumor necrosis factor-, (TNF-,) is one of the key cytokines elicited by host macrophages upon challenge with pathogenic mycobacteria. Infection of human peripheral blood mononuclear cells or the murine macrophage cell line J774A,1 with Mycobacterium avium induced activation of the mitogen-activated protein kinases (MAPKs) ERK1/2, p38 and c-Jun N-terminal kinase. U0126, an MEK-specific inhibitor, abrogated M. avium -induced TNF-, secretion. Transfection of cells with dominant-negative MEK1 led to the suppression of TNF-, release in M. avium -challenged macrophages. M. avium activated p38 MAPK and use of the p38 MAPK inhibitor, SB203580, revealed that the p38 signaling pathway negatively regulates activation of ERK1/2 and release of TNF-,. Taken together, these results provide evidence that M. avium -induced TNF-, release from macrophages depends on an interplay between the ERK1/2 and the p38 MAPK signaling pathways. [source]

Adaptation of the brucellae to their intracellular niche

MOLECULAR MICROBIOLOGY, Issue 3 2004
R. Martin Roop II
Summary Members of the bacterial genus Brucella are facultative intracellular pathogens that reside predominantly within membrane-bound compartments within two host cell types, macrophages and placental trophoblasts. Within macrophages, the brucellae route themselves to an intracellular compartment that is favourable for survival and replication, and they also appear to be well-adapted from a physiological standpoint to withstand the environmental conditions encountered during prolonged residence in this intracellular niche. Much less is known about the interactions of the Brucella with placental trophoblasts, but experimental evidence suggests that these bacteria use an iron acquisition system to support extensive intracellular replication within these host cells that is not required for survival and replication in host macrophages. Thus, it appears that the brucellae rely upon the products of distinct subsets of genes to adapt successfully to the environmental conditions encountered within the two cell types within which they reside in their mammalian hosts. [source]

IL-10 down-regulates costimulatory molecules on Mycobacterium tuberculosis -pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2004
S. DE LA BARRERA
SUMMARY Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFN, is a key cytokine responsible for macrophage activation during Mycobacterium tuberculosis (Mtb) infection while IL-10 is associated with suppression of cell mediated immunity in intracellular infection. In this paper we evaluated the role of IFN, and IL-10 on the function of cytotoxic T cells (CTL) and on the modulation of costimulatory molecules in healthy controls and patients with active tuberculosis (TB). , -irradiated- Mtb (i- Mtb) induced IL-10 production from CD14+ cells from TB patients. Moreover, CD3+ T cells of patients with advanced disease also produced IL-10 after i- Mtb stimulation. In healthy donors, IL-10 decreased the lytic activity of CD4+ and CD8+ T cells whereas it increased ,, -mediated cytotoxicity. Furthermore, we found that the presence of IL-10 induced a loss of the alternative processing pathways of antigen presentation along with a down-regulation of the expression of costimulatory molecule expression on monocytes and macrophages from healthy individuals. Conversely, neutralization of endogenous IL-10 or addition of IFN, to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8+ CTL together with an up-regulation of CD54 and CD86 expression on target cells. Moreover, we observed that macrophages from TB patients could use alternative pathways for i- Mtb presentation. Taken together, our results demonstrate that the presence of IL-10 during Mtb infection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages. [source]