scholarly journals Skin Test Performed with Highly Purified Mycobacterium tuberculosis Recombinant Protein Triggers Tuberculin Shock in Infected Guinea Pigs

2005 ◽  
Vol 73 (6) ◽  
pp. 3301-3306 ◽  
Author(s):  
Stephen T. Reece ◽  
Nicole Stride ◽  
Pamela Ovendale ◽  
Steven G. Reed ◽  
Antonio Campos-Neto
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Recombinant Protein ◽  
Skin Test ◽  
Guinea Pigs ◽  
Lung Parenchyma ◽  
Necrosis Factor Alpha ◽  
Vaccine Candidates ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Present Experimental Evidence

ABSTRACT Tuberculin shock due to inoculation of Mycobacterium tuberculosis antigens in patients with tuberculosis is a serious syndrome originally described over 100 years ago by Robert Koch. Here, we present experimental evidence that a single M. tuberculosis recombinant protein, CFP-10, triggers this syndrome. Intradermal inoculation of CFP-10 elicits in M. tuberculosis-infected mice high levels of serum tumor necrosis factor alpha and causes tuberculin shock in infected guinea pigs characterized by hypothermia and death within 6 to 48 h after the antigen inoculation. Autopsies of these animals revealed intense polycythemia and hemorrhagic patches in the lung parenchyma, a pathological observation consistent with tuberculin shock. These results point to the possible occurrence of tuberculin shock in sensitive individuals inoculated with highly purified M. tuberculosis recombinant proteins as vaccine candidates or skin test reagents.

scholarly journals HLA-B*35-Restricted CD8+-T-Cell Epitope in Mycobacterium tuberculosis Rv2903c

2002 ◽  
Vol 70 (2) ◽  
pp. 981-984 ◽  
Author(s):  
Michèl R. Klein ◽  
Abdulrahman S. Hammond ◽  
Steve M. Smith ◽  
Assan Jaye ◽  
Pauline T. Lukey ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Mycobacterial Antigens ◽  
Necrosis Factor

ABSTRACT Few human CD8+ T-cell epitopes in mycobacterial antigens have been described to date. Here we have identified a novel HLA-B*35-restricted CD8+ T-cell epitope in Mycobacterium tuberculosis Rv2903c based on a reverse immunogenetics approach. Peptide-specific CD8 T cells were able to kill M. tuberculosis-infected macrophages and produce gamma interferon and tumor necrosis factor alpha.

scholarly journals Factors Associated with Severe Granulomatous Pneumonia in Mycobacterium tuberculosis-Infected Mice Vaccinated Therapeutically with hsp65 DNA

2005 ◽  
Vol 73 (8) ◽  
pp. 5189-5193 ◽  
Author(s):  
Jennifer L. Taylor ◽  
Diane J. Ordway ◽  
JoLynn Troudt ◽  
Mercedes Gonzalez-Juarrero ◽  
Randall J. Basaraba ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ex Vivo ◽  
Interleukin 10 ◽  
Lung Pathology ◽  
Necrosis Factor Alpha ◽  
Cd8 Cells ◽  
Factor Alpha ◽  
Cell Gene ◽  
Granulomatous Pneumonia ◽  
Necrosis Factor

ABSTRACT Resistant C57BL/6 mice infected in the lungs with Mycobacterium tuberculosis and then therapeutically vaccinated with Mycobacterium leprae-derived hsp65 DNA develop severe granulomatous pneumonia and tissue damage. Analysis of cells accumulating in the lungs of these animals revealed substantial increases in T cells secreting tumor necrosis factor alpha and CD8 cells staining positive for granzyme B. Stimulation of lung cells ex vivo revealed very high levels of interleukin-10, some of which was produced by B-1 B cells. This was probably an anti-inflammatory response, since lung pathology was dramatically worsened in B-cell gene-disrupted mice.

scholarly journals Effect of Deletion or Overexpression of the 19-Kilodalton Lipoprotein Rv3763 on the Innate Response to Mycobacterium tuberculosis

2005 ◽  
Vol 73 (10) ◽  
pp. 6831-6837 ◽  
Author(s):  
Graham R. Stewart ◽  
Katalin A. Wilkinson ◽  
Sandra M. Newton ◽  
Susan M. Sullivan ◽  
Olivier Neyrolles ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Surface Expression ◽  
Innate Immune ◽  
Innate Response ◽  
Necrosis Factor Alpha ◽  
Histocompatibility Complex ◽  
Factor Alpha ◽  
Multicopy Vector ◽  
Necrosis Factor

ABSTRACT The 19-kDa lipoprotein of Mycobacterium tuberculosis is an important target of the innate immune response. To investigate the immune biology of this antigen in the context of the whole bacillus, we derived a recombinant M. tuberculosis H37Rv that lacked the 19-kDa-lipoprotein gene (Δ19) and complemented this strain by reintroduction of the 19-kDa-lipoprotein gene on a multicopy vector to produce Δ19::pSMT181. The Δ19 strain multiplied less well than Δ19::pSMT181 in human monocyte-derived macrophages (MDM) (P = 0.039). Surface expression of major histocompatibility complex class II molecules was reduced in phagocytes infected with M. tuberculosis; this effect was not seen in cells infected with Δ19. Δ19 induced lower interleukin 1β (IL-1β) secretion from monocytes and MDM. Overexpression of the 19-kDa protein increased IL-1β, IL-12p40, and tumor necrosis factor alpha secretion irrespective of phagocyte maturity. These data support reports that the 19-kDa lipoprotein has pleiotropic effects on the interaction of M. tuberculosis with phagocytes. However, this analysis indicates that in the context of the whole bacillus, the 19-kDa lipoprotein is only one of a number of molecules that mediate the innate response to M. tuberculosis.

scholarly journals Enhancement of Mycobacterium tuberculosis-Induced Tumor Necrosis Factor Alpha Production from Primary Human Monocytes by an Activated T-Cell Membrane-Mediated Mechanism

2001 ◽  
Vol 69 (11) ◽  
pp. 6580-6587 ◽  
Author(s):  
Jan Warwick-Davies ◽  
Amanda J. Watson ◽  
George E. Griffin ◽  
Sanjeev Krishna ◽  
Robin J. Shattock
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Mycobacterium tuberculosis alone induces small, donor-variable amounts of tumor necrosis factor alpha (TNF-α) from primary human monocytes in vitro. However, TNF-α release is increased 5- to 500-fold when fixed activated T cells (FAT) or their isolated, unfixed membranes are added to this system. This FAT-induced synergy was at least as potent as that induced by gamma interferon (IFN-γ) at 100 U/ml. FAT-enhanced TNF-α production is at least in part transcriptionally mediated, as reflected by quantitative changes in TNF-α mRNA between 2 and 6 h poststimulation. Unlike IFN-γ-cocultured cells, FAT-treated monocytes appeared not to have enhanced TNF-α message stability, suggesting that de novo transcription may be involved in this effect. Furthermore, M. tuberculosis alone induced only minimal DNA binding of monocyte NF-κB, but cells treated with M. tuberculosis and FAT potentiated NF-κB activity more effectively. It is therefore possible that one mechanism by which FAT synergize with M. tuberculosis to stimulate TNF-α production is via NF-κB-enhanced transcription. These data strongly suggest that in the interaction of cells involved in the immune response to M. tuberculosis, T-cell stimulation of monocyte TNF-α production involves a surface membrane interaction(s) as well as soluble mediators.

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