Cell cycle lung granuloma tuberculosis

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), is one of the most successfully adapted human pathogens. Human-to-human transmission occurs at high rates through aerosols containing bacteria, but the pathogen evolved prior to the establishment of crowded populations. Mtb has developed a particular strategy to ensure persistence in the host until an opportunity for transmission arises. It has refined its lifestyle to obviate the need for virulence factors such as capsules, flagella, pili, or toxins to circumvent mucosal barriers...

During the dormant phase of tuberculosis, Mycobacterium tuberculosis persists in lung granulomas by residing in foamy macrophages (FM) that contain abundant lipid bodies (LB) in their cytoplasm, allowing bacilli to accumulate lipids as intracytoplasmic lipid inclusions (ILI). An experimental model of FM is presented where bone marrow-derived mouse macrophages are infected with M. avium and exposed to very-low-density lipoprotein (VLDL) as a lipid source. Quantitative analysis of detailed electron microscope observations showed the following results...

During the dormant phase of tuberculosis, Mycobacterium tuberculosis persists in lung granulomas by residing in foamy macrophages (FM) that contain abundant lipid bodies (LB) in their cytoplasm, allowing bacilli to accumulate lipids as intra-cytoplasmic lipid inclusions (ILI). An experimental model of FM is presented where bone marrow-derived mouse macrophages are infected with M. avium and exposed to very low density lipoprotein (VLDL) as a lipid source. Quantitative analysis of detailed electron microscope observations showed the following results: (i) Macrophages became foamy and mycobacteria formed ILI, for which host triacylglycerides, rather than cholesterol, was essential; (ii) Lipid transfer occurred via mycobacteria-induced fusion between LB and phagosomes; (iii) Mycobacteria showed a thinned cell wall and became elongated; (iv) Upon removal of VLDL, LB and ILI declined within hours and simultaneous resumption of mycobacterial division restored the number of mycobacteria to the same level as that found in untreated control macrophages...

Confrontation between invading microbial pathogens and host defense systems involves intricate cellular and molecular interactions. Here we discuss the virulence factors as trumps, overriding the contest in favor of the tubercle bacillus (Mycobacterium tuberculosis). It evolved a number of molecular constituents, which can interfere with antigen presentation and Toll receptor function, thus impairing immune defenses. It also evolved stress responses, which can drive its cell cycle into a non-replicating, low metabolic mode...

It is firmly established that the allelic composition of the H-2 complex has a prominent impact on the course of tuberculosis (TB) infection in mice, including granuloma formation, mycobacterial spread in the lungs, and the dynamics of mortality. Although intuitively obvious, the role of long-term specific T cell responses in the expression of corresponding phenotypes is poorly understood. In this study we have compared polyclonal lymph node cell response (cell yield, proliferation, surface markers, IL-4/interferon-gamma (IFN-gamma) production) to Mycobacterium tuberculosis H37Rv sonicate in repeated 10-day cycles of stimulation/rest between H-2 congenic IE-negative mouse strains, categorized on the basis of mortality following lethal challenge as TB-susceptible (C57B1/6), TB-resistant (4R) and BCG non-protected (B10...

In sarcoidosis, pleomorphic chromogens (PCs) occur as multivariate pigmented elements within sinusoids of lymph nodes (sinusoidal phase) and as tiny "round bodies" detectable in granulomas (generalized phase). The sinusoidal phase occurs in other conditions as well and characteristically contains yeastlike bodies also known as H-W bodies. To elucidate the antigenic profile of all variant forms, 28 cases of sarcoidosis (series A) and 14 cases of malignancy associated sinus histiocytosis (series B) were studied immunohistochemically with panels of various antibodies, including antimycobacterial MAbs specific for M tuberculosis complex (TB68, TB71), for M...

Granulomas are a local formation of specific cells including macrophages and lymphocytes revealing a chronic inflammatory reaction against infection, often due to intracellular agents. Granulomas can be composed of macrophages (foreign body reaction), epithelioid cells (immune granulomas of sarcoidosis, tuberculosis), or Langerhans' cells (histiocytosis X). In immune granulomas, the epithelioid cells derived from activated macrophages are found at the centre of the granuloma associated with CD4+ T-lymphocytes, while the periphery is mainly populated with CD8+ T-lymphocytes...