Reduced TNF-α and IFN-γ responses to Central Asian strain 1 and Beijing isolates of Mycobacterium tuberculosis in comparison with H37Rv strain

2009 ◽  
Vol 103 (6) ◽  
pp. 581-587 ◽  
Author(s):  
Mahnaz Tanveer ◽  
Zahra Hasan ◽  
Akbar Kanji ◽  
Rabia Hussain ◽  
Rumina Hasan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Asian Strain ◽  
Central Asian ◽  
H37rv Strain ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals Mycobacterium tuberculosis clinical isolates of the Beijing and East-African Indian lineage induce fundamentally different host responses in mice compared to H37Rv

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bas C. Mourik ◽  
Jurriaan E. M. de Steenwinkel ◽  
Gerjo J. de Knegt ◽  
Ruth Huizinga ◽  
Annelies Verbon ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Isolates ◽  
Host Responses ◽  
East African ◽  
Protein Levels ◽  
H37rv Strain ◽  
Tnf Α ◽  
Functionally Impaired ◽  
Ifn Γ ◽  
Mycobacterial Strain

AbstractSubstantial differences exist in virulence among Mycobacterium tuberculosis strains in preclinical TB models. In this study we show how virulence affects host responses in mice during the first four weeks of infection with a mycobacterial strain belonging to the Beijing, East-African-Indian or Euro-American lineage. BALB/c mice were infected with clinical isolates of the Beijing-1585 strain or the East-African Indian (EAI)-1627 strain and host responses were compared to mice infected with the non-clinical H37Rv strain of the Euro-American lineage. We found that H37Rv induced a ‘classical’ T-cell influx with high IFN-γ levels, while Beijing-1585 and EAI-1627 induced an influx of B-cells into the lungs together with elevated pulmonary IL-4 protein levels. Myeloid cells in the lungs appeared functionally impaired upon infection with Beijing-1585 and EAI-1627 with reduced iNOS and IL-12 expression levels compared to H37Rv infection. This impairment might be related to significantly reduced expression in the bone marrow of IFN-γ, TNF-α and IFN-β in mice infected with Beijing-1585 and EAI-1627, which could be detected from the third day post infection onwards. Our findings suggest that increased virulence of two clinical isolates compared to H37Rv is associated with a fundamentally different systemic immune response, which already can be detected early during infection.

scholarly journals Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

2011 ◽  
Vol 55 (12) ◽  
pp. 5654-5659 ◽  
Author(s):  
Asho Ali ◽  
Rumina Hasan ◽  
Kauser Jabeen ◽  
Nusrat Jabeen ◽  
Ejaz Qadeer ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
East African ◽  
Content Type ◽  
Diagnostic Assays ◽  
Asian Strain ◽  
Central Asian ◽  
Extensive Drug Resistance ◽  
Detection Of Mutations

ABSTRACTThe increasing incidence of extensively drug-resistant (XDR)Mycobacterium tuberculosisin high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDRM. tuberculosisstrains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the “hot-spot” regions ofrpoB,katG,inhA,ahpC,gyrA,gyrB, andrrsgenes in 50 XDRM. tuberculosisstrains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDRM. tuberculosisstrains would be undetected if only these common hot-spot regions were tested. The frequencies of resistance-conferring mutations were found to be comparable among all XDRM. tuberculosisstrain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDRM. tuberculosisstrains.

scholarly journals Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

2015 ◽  
Vol 83 (5) ◽  
pp. 2118-2126 ◽  
Author(s):  
Truc Hoang ◽  
Else Marie Agger ◽  
Joseph P. Cassidy ◽  
Jan P. Christensen ◽  
Peter Andersen
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd4 T Cells ◽  
Protein Energy Malnutrition ◽  
T Cell Subsets ◽  
Content Type ◽  
Protein Energy ◽  
Tnf Α ◽  
Ifn Γ

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse ofMycobacterium tuberculosis, as well as increased pathology, in bothMycobacterium bovisBCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ+TNF-α+and IFN-γ+cells). PEM duringM. tuberculosisinfection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine againstM. tuberculosisinfection.

scholarly journals Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype

2013 ◽  
Vol 81 (10) ◽  
pp. 3750-3756 ◽  
Author(s):  
Arjan van Laarhoven ◽  
Jornt J. Mandemakers ◽  
Johanneke Kleinnijenhuis ◽  
Mimount Enaimi ◽  
Ekta Lachmandas ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Selective Advantage ◽  
Beijing Genotype ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Tnf Α ◽  
Evolutionary Success ◽  
Ifn Γ

ABSTRACTOne of the most widespread clades ofMycobacterium tuberculosisworldwide, the Beijing genotype family, consists of ancient (atypical) and modern (typical) strains. Modern Beijing strains outcompete ancient strains in terms of prevalence, while reserving a higher degree of genetic conservation. We hypothesize that their selective advantage lies in eliciting a different host immune response. Bead-disrupted lysates of a collection of differentM. tuberculosisstrains of the modern (n= 7) or ancient (n= 7) Beijing genotype, as well as the Euro-American lineage (n= 6), were used for induction ofex vivocytokine production in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals. Hierarchical clustering and multivariate regression analyses were used to study possible differences in production of nine cytokines. Modern and ancientM. tuberculosisBeijing genotypes induced different cytokine signatures. Overall induction of interleukin-1β (IL-1β), gamma interferon (IFN-γ), and IL-22 was 38 to 40% lower after stimulation with modern Beijing strains (correctedPvalues of <0.0001, 0.0288, and 0.0002, respectively). Euro-American reactivation strains induced 2-fold more TNF-α production than both types of Beijing strains. The observed differences in cytokine induction point to a reduction in proinflammatory cytokine response as a possible contributing factor to the evolutionary success of modern Beijing strains.

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