Macrophages play an essential role in the immune response to Mycobacterium tuberculosis (Mtb). Previous transcriptome surveys, by means of micro- and macroarrays, investigated the cellular gene expression profile during the early phases of infection (within 48 hr). However, Mtb remains within the host macrophages for a longer period, continuing to ...

BACKGROUND: Interleukin (IL)-32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system. METHODS AND FINDINGS: In the present study, freshly obtained human peripheral blood mononuclear ...

Lysophosphatidic acid (LPA) is a polar lipid metabolite which is involved in a wide range of biological processes, including cell proliferation and migration, wound healing, and increase of endothelial permeability. The present study reports evidences showing that LPA is able to enhance the antimicrobial activity of human macrophages and of ...

BACKGROUND: Tumor necrosis factor (TNF) plays a pathogenic role in rheumatoid arthritis but is essential for antimycobacterial host defenses. The risk of reactivation of latent Mycobacterium tuberculosis infection is greater with the TNF monoclonal antibody infliximab than with the soluble TNF receptor etanercept. The basis of this difference is not ...

Little is known regarding the early events of infection of humans with Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of tuberculosis, with strong similarities to human tuberculosis. In this study, eight cynomolgus macaques were infected bronchoscopically with low-dose M. tuberculosis; clinical, immunologic, microbiologic, and pathologic events were assessed ...

Autophagy is a homeostatic process whereby cytosol or intracellular organelles are sequestered by a double membrane structure termed autophagosome for subsequent delivery to lysosomes and degradation. Autophagy takes part in cell survival and death and has been implicated in development, aging, neurodegeneration and cancer. The newly discovered specialized role of ...

A crucial step in infection is the initial attachment of a pathogen to host cells or tissue. Mycobacterium tuberculosis has evolved multiple strategies for establishing an infection within the host. The pulmonary microenvironment contains a complex milieu of pattern recognition molecules of the innate immune system that play a role ...

p-Hydroxybenzoic acid derivatives (p-HBADs) are glycoconjugates secreted by all Mycobacterium tuberculosis isolates whose contribution to pathogenicity remains to be determined. The pathogenicity of three transposon mutants of M. tuberculosis deficient in the biosynthesis of some or all forms of p-HBADs was studied. Whilst the mutants grew similarly to the wild-type ...

Effective host defense against Mycobacterium tuberculosis requires the induction of Th1 cytokine responses. We investigated the regulated expression and functional role of the inducible costimulator (ICOS), a receptor known to regulate Th cytokine production, in the context of human tuberculosis. Patients with active disease, classified as high responder (HR) or ...

We generated several attenuated recombinant influenza A vectors expressing the Mycobacterium tuberculosis early secretory antigenic target (ESAT-6) protein. The ESAT-6 protein was recently identified as one of the most promising protective antigens for cell-mediated immunity. The obtained vectors appeared to be capable of inducing ESAT-6 specific Th1 immune response in ...

It is well known that the majority of healthy individuals exposed to Mycobacterium tuberculosis do not become clinically ill. We have previously shown that in recently exposed healthy contacts of tuberculosis (TB) patients, a strong immune response to the M. tuberculosis 6-kDa early secreted antigenic target (ESAT-6) virulence factor correlated ...

A marquee feature of the powerful human pathogen Mycobacterium tuberculosis is its macrophage parasitism. The intracellular survival of this microorganism rests upon its ability to arrest phagolysosome biogenesis, avoid direct cidal mechanisms in macrophages, and block efficient antigen processing and presentation. Mycobacteria prevent Rab conversion on their phagosomes and elaborate ...

Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic ...

Changes that may modify the capacity of macrophages to control mycobacterial growth could favour the reactivation of bacillary proliferation within protective granulomas developed in response to mycobacterial infection. There is increasing evidence that diesel exhaust particles (DEPs) could suppress some macrophage functions, but it is not known whether DEPs may ...

We previously reported that macrophage exposure to attenuated strains of pathogenic mycobacteria at multiplicities of infection (MOI) < or = 10 triggers TNF-alpha-mediated apoptosis which reduces the viability of intracellular bacilli. Virulent strains were found to suppress macrophage apoptosis, and it was proposed that apoptosis is an innate defense against ...

Mycobacteria tuberculosis infects about one third of the world population in their life times and causes millions of deaths each year. M. tuberculosis has a unique capability to circumvent the bactericidal activities of macrophages - the frontline defenders of the host immunity. New understanding of this mechanism has positioned scientists ...

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an intracellular pathogen that is known to parasitize macrophages. MAP is the known etiological agent of Johne's disease and implicated in the etiology of Crohn's disease. MATERIAL/METHODS: In this study, the survival of human-derived MAP isolate following phagocytosis was evaluated using murine macrophage ...

Sarcoidosis (SA) is a granulomatous disorder of an unknown etiology. Mycobacterium tuberculosis heat shock proteins (Mtb-hsp), considered as causative agents, play an important role in apoptosis. A role for apoptosis has been proposed in pathogenesis of SA and tuberculosis (TB) granuloma formation but results remain controversial. Differences in Mtb-hsp-induced apoptosis ...

Buruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. ...

Mycobacterium leprae and Mycobacterium tuberculosis are successful intracellular pathogens which down regulate host immune responses. T-cell interferon-gamma (IFNgamma) and macrophage tumour necrosis factor-alpha (TNFalpha) activate chemokines such as, C-C chemokine ligand-2 (CCL2) and CCL5, which play a role in granuloma formation. Lepromatous leprosy is characterized by defective granulomas with lowered ...

A potent Th1 immune response is critical to the control of tuberculosis. The impact of an additive Th2 response on the course of disease has so far been insufficiently characterized, despite increased morbidity after co-infection with Mycobacterium tuberculosis and Th2-eliciting helminths and possible involvement of Th2 polarization in reactivation of ...

Mycobacterium tuberculosis is a highly successful pathogen that can persist and cause disease despite an immune response. One potential mechanism for resisting elimination is by inhibiting the action of IFN-gamma. We have previously shown that live M. tuberculosis inhibits selected macrophage responses to IFN-gamma, and that purified M. tuberculosis 19-kDa ...

Interactions of Mycobacterium tuberculosis with macrophages have long been recognized to be crucial to the pathogenesis of tuberculosis. The role of non-phagocytic cells is less well known. We have discovered a M. tuberculosis surface protein that interacts specifically with non-phagocytic cells, expresses hemagglutination activity and binds to sulfated glycoconjugates. It ...

The granulomatous reaction is the hallmark of the host response to infection with Mycobacterium tuberculosis. Despite its apparent importance to host defence against the tubercle bacillus, the granulomatous response remains to be completely defined. The present study used histological, immunohistochemical and flow-cytometric analyses to characterize pulmonic granulomatous tissues of tuberculous ...

The kinetics of macrophage and T lymphocyte apoptosis were determined in a well-characterized mouse model of pulmonary tuberculosis, comparing strains of intermediate (H37Rv) and high virulence (Beijing strain, code 9501000). Both strains induced a high percentage of apoptotic activated macrophages at days 1 and 3 post infection, although this was ...

PURPOSE OF REVIEW: The purpose of this review is to describe the epidemiology, clinical features, putative immune mechanisms and management of immune reconstitution inflammatory syndrome (IRIS) using data published in the last 2 years. RECENT FINDINGS: Ever more conditions are reported as IRIS events. These most frequently occur with mycobacterial ...

It has recently become feasible to quantify all mRNAs encoded by the genomes of bacterial pathogens and their eukaryotic host cells and to apply this approach to study the interaction of Mycobacterium tuberculosis with its primary host cell, the macrophage. These studies helped to identify regulatory circuits which mediate adaptation ...

The course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Histamine plays an important role in various processes, including cell division, metabolism, and apoptosis, and it modulates innate and adaptive immune ...

Immunity to Mycobacterium tuberculosis infection is critically dependent on the timely priming of T effector lymphocytes and their efficient recruitment to the site of mycobacterial implantation in the lung. E-, P-, and L-selectin counterreceptors control lymphocyte homing to lymph nodes and leukocyte trafficking to peripheral sites of acute inflammation, their ...

Pathogenic mycobacteria, in particular Mycobacterium tuberculosis, the causative agent of tuberculosis, have the remarkable capacity to circumvent destruction within one of the most hostile cell types of a vertebrate host: the macrophage. The ability of pathogenic mycobacteria to survive inside macrophages has been known for more than 30 years; yet, ...

Studying infections with Mycobacterium avium in mouse models has allowed the dissection of the antimycobacterial pathways of the mammalian host. Whereas the paradigm of cell-mediated immunity to intracellular pathogens has been confirmed, namely with regard to the pivotal roles of CD4+ T cells, macrophages, and the IL12-IFNgamma cytokine axis, atypical ...

There are more cases of tuberculosis in the world today than at any other time in history. The global epidemic has generated intense interest into the immunological mechanisms that control infection. Although CD4+ T cells play a critical role in host immunity to Mycobacterium tuberculosis, there is considerable interest in ...

Mycobacterium tuberculosis (Mtb) invades the lung via an airborne pathway, and the bacteria reach the lung alveoli and are then engulfed by alveolar macrophages in innate immunity, which uses germline-encoded pattern recognition receptors such as the mannose receptor and Toll-like receptor for recognition of the pathogen. Mtb can survive in ...

Mycobacterium avium is a significant cause of morbidity and mortality in AIDS patients. M. avium can be isolated as three major morphotypes: smooth-transparent (SmT ), smooth-opaque (SmO) and rough (Rg). Studies indicate that many Rg isolates lack or have modified glycopeptidolipids (GPLs). GPLs are major surface constituents of the M. ...

BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease (JD) persistently infects and survives within the host macrophages. While it is established that substantial genotypic variation exists among MAP, evidence for the correlates that associate specific MAP genotypes with clinical or sub-clinical disease phenotypes is presently unknown. ...

Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-alpha as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal (MG), a small and reactive molecule that is usually a physiological product of various ...

CXC chemokine release can be modulated by Th2-derived cytokines. Interleukin(IL)-4 is one of the cytokines that are the hallmark of the Th-2 response, and plays an important role in human tuberculosis. In the current study, we investigated the effect of IL-4 on chemokine production by human epithelial cells infected with ...

Cytokine-mediated regulation of chronic intestinal helminth infections is well documented. The present study reports the serum cytokine responses in 38 ascariasis (stool samples positive for Ascaris lumbricoides ova) and toxocariasis (seropositive) patients, 8 ascariasis-positive and toxocariasis-seronegative patients, 22 endemic, normal, healthy subjects residing in areas hyperendemic for ascariasis and 16 ...

RATIONALE: T-cell responses during tuberculosis (TB) help contain Mycobacterium tuberculosis in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune responses in patients with TB suggest the presence of regulatory activity. CD4+CD25(high) regulatory T cells mediate suppressed cellular immunity ...

PURPOSE OF REVIEW: As an essential part of the hygiene hypothesis, the association between exposure to mycobacterial components and the prevention, development and severity of atopic diseases has not been fully understood. The current status on the causal-effect link of this relationship and the potential use of mycobacterial adjuvants as ...

The ability of CD8+ T cells to kill intracellular pathogens depends upon their capacity to attract infected cells as well as their secretion of cytolytic and antimicrobial effector molecules. We examined the Ag-induced expression of three immune effector molecules contained within cytoplasmic granules of human CD8+ T cells: the chemokine ...

ATP, which serves as a mediator of intramacrophage signaling pathways through purinoceptors, is known to potentiate macrophage antimycobacterial activity. In this study we examined the effects of ATP in potentiating host resistance to Mycobacterium avium complex (MAC) infection in mice undergoing treatment with a drug regimen using clarithromycin and rifamycin ...

Although corticosteroids are recommended as adjunctive therapy for tuberculous meningitis, the mechanism underlying their beneficial effect is poorly understood. In this study, human microglia and astrocytes were infected with Mycobacterium tuberculosis H37Rv, and cytokine and chemokine expression was examined with and without dexamethasone treatment. Microglia were the principal cells infected ...

In this study, we investigated the ability of four clinical isolates of Mycobacterium tuberculosis representing a range of virulence for their capacity to grow in bone marrow-derived macrophages. The rate of growth of each of the isolates in macrophages reflected their known virulence, but the most virulent isolates strongly induced ...

Adoptively transferred dendritic cells presenting antigens derived from different pathogens have been shown to elicit specific T cell responses and to induce protective antibacterial immunity. We describe here the induction of high levels of protective immunity in mice using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis. We provide ...

LPO and apoptosis in blood mononuclear cells were studied in patients with pulmonary tuberculosis before and during treatment with standard chemotherapeutics. Pulmonary tuberculosis was accompanied by LPO activation and intensification of apoptosis in lymphocytes and monocytes. These changes were observed before and after the course of intensive care. The intensity ...

The cell envelope of mycobacteria is a complex structure that plays an important role in the interactions of the cell with its environment and in the protection against the antimicrobial activity of the immune system. Glycopeptidolipids (GPLs) are species- or type species-specific glycolipids that are present at the surface of ...

Infection with Mycobacterium tuberculosis is one of the leading causes of death worldwide. Recognition of M. tuberculosis by pattern recognition receptors is crucial for activation of both innate and adaptive immune responses. In the present study, we demonstrate that nucleotide-binding oligomerization domain 2 (NOD2) and Toll-like receptors (TLRs) are two ...

Transcription profiling of genes encoding components of the respiratory chain and the ATP synthesizing apparatus of Mycobacterium tuberculosis was conducted in vivo in the infected mouse lung, and in vitro in bacterial cultures subjected to gradual oxygen depletion and to nitric oxide treatment. Transcript levels changed dramatically as infection progressed ...

The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the expression ...