scholarly journals The emergence of latent infection in the early evolution of Mycobacterium tuberculosis

2016 ◽  
Vol 283 (1831) ◽  
pp. 20160499 ◽  
Author(s):  
Rebecca H. Chisholm ◽  
Mark M. Tanaka
Keyword(s):  
Mathematical Model ◽  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Genetic Variation ◽  
Natural Selection ◽  
Natural History ◽  
Latent Infection ◽  
Human Populations ◽  
Safe Harbour ◽  
Active Disease

Mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. From the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a détente with the host immune response. However, a small fraction of latent infections reactivate to the disease state. Thus, latency has been argued to provide a safe harbour for future infections which optimizes the persistence of M. tuberculosis in human populations. Yet, if a pathogen begins interactions with humans as an active disease without latency, how could it begin to evolve latency properties without incurring an immediate reproductive disadvantage? We address this question with a mathematical model. Results suggest that the emergence of tuberculosis latency may have been enabled by a mechanism akin to cryptic genetic variation in that detrimental latency properties were hidden from natural selection until their expression became evolutionarily favoured.

scholarly journals A Spotlight on Liquefaction: Evidence from Clinical Settings and Experimental Models in Tuberculosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Pere-Joan Cardona
Keyword(s):  
Immune Response ◽  
Natural History ◽  
Experimental Models ◽  
Point Of View ◽  
Clinical Settings ◽  
Cavity Formation ◽  
Stochastic Effect ◽  
History Of ◽  
Mechanical Factors ◽  
Active Disease

Liquefaction is one of the most intriguing aspects of human tuberculosis. It is a major cause of the transition from the infection to active disease (tuberculosis, TB) as well as the transmission ofM. tuberculosisto other persons. This paper reviews the natural history of liquefaction in humans from a pathological and radiological point of view and discusses how the experimental models available can be used to address the topic of liquefaction and cavity formation. Different concepts that have been related to liquefaction, from the influence of immune response to mechanical factors, are reviewed. Synchronic necrosis or apoptosis of infected macrophages in a close area, together with an ineffective fibrosis, appears to be clue in this process, in which macrophages, the immune response, and bacillary load interact usually in a particular scenario: the upper lobes of the lung. The summary would be that even if being a stochastic effect, liquefaction would result if the organization of the intragranulomatous necrosis (by means of fibrosis) would be disturbed.

scholarly journals Characterization of genetic variation and natural selection at the arylamineN-acetyltransferase genes in global human populations

2011 ◽  
Vol 12 (11) ◽  
pp. 1545-1558 ◽  
Author(s):  
Holly M Mortensen ◽  
Alain Froment ◽  
Godfrey Lema ◽  
Jean-Marie Bodo ◽  
Muntaser Ibrahim ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Natural Selection ◽  
Human Populations

scholarly journals Accuracy of QuantiFERON-TB Gold Plus Test for Diagnosis of Mycobacterium tuberculosis Infection in Children

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Danilo Buonsenso ◽  
Giovanni Delogu ◽  
Clelia Perricone ◽  
Roberta Grossi ◽  
Angela Careddu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Latent Infection ◽  
Cross Sectional Study ◽  
Mycobacterium Tuberculosis Infection ◽  
Cross Sectional ◽  
Content Type ◽  
Latent Tb ◽  
Latent Tb Infection ◽  
Microbiological Analyses ◽  
Active Disease

ABSTRACT Compared to its predecessor QuantiFERON-TB Gold In Tube (QFT-IT), QuantiFERON-TB Gold Plus (QFT-Plus) contains an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T cells. The ability to discriminate CD4+ and CD8+ responses is suggested to be useful in differentiating stages of Mycobacterium tuberculosis infection. While QFT-Plus has already been evaluated in adults, there are not enough data in children evaluated for suspected active tuberculosis (TB) or latent TB infection (LTBI). A prospective cross-sectional study was conducted among children aged 0 to 17 years who were evaluated for suspected active TB or screened for LTBI. All children underwent QFT-Plus and further clinical, radiological, and/or microbiological analyses according to clinical scenario. Of the 198 children enrolled, 43 (21.7%) were tested because of suspicion of active TB. A total of 12/43 (27.9%) were diagnosed with active TB, and among these, 10/12 (83.3%) had a positive QFT-Plus assay. Of the 155 children screened for LTBI, 18 (11.6%) had a positive QFT-Plus, and 5 (2.5%) had an indeterminate result. TB1 and TB2 quantitative responses were not able to discriminate active disease from latent infection. The percent agreement between TB1 and TB2 was 100%. QFT-Plus assay showed good sensitivity for active TB and was particularly useful for the evaluation of children with suspected LTBI, giving a low rate of indeterminate results in this group. More studies are needed to properly evaluate QFT-Plus ability in discriminating active disease from latent infection.

scholarly journals Mycobacterium tuberculosis-specific CD8+T cells are functionally and phenotypically different between latent infection and active disease

2013 ◽  
Vol 43 (6) ◽  
pp. 1568-1577 ◽  
Author(s):  
Virginie Rozot ◽  
Selena Vigano ◽  
Jesica Mazza-Stalder ◽  
Elita Idrizi ◽  
Cheryl L. Day ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd8 T Cells ◽  
Latent Infection ◽  
Active Disease

Models of the evolution of dominance

1968 ◽  
Vol 171 (1022) ◽  
pp. 127-143 ◽  
Keyword(s):  
Mathematical Model ◽  
Genetic Variation ◽  
Natural Selection ◽  
Genetic Variance ◽  
Deleterious Mutation ◽  
The Other ◽  
Wild Type ◽  
Selective Forces ◽  
Mutant Homozygote ◽  
Selective Effects

There are three essentially different models to explain how dominance might gradually evolve by natural selection. In Fisher’s model, the wild-type evolves dominance in response to the occurrence of deleterious mutation s: genetic variations in the expression of the mutant heterozygote will be selected to raise its fitness an d produce dominance or over-dominance. The rate of this selection is slow and depends on what the fitness of the heterozygote will be at its optimum. In Parsons & Bodmer’s model, the fitness of an advantageous mutant hetero ¬ zygote is raised up to or above that of the mutant homozygote while the mutation is spreading through a population. Whether dominance or over-dominance is reached depends on the heterozygote’s genetic variance and optimum fitness. In both these models, the variations in the mutant heterozygote must be caused by modifiers with more or less neutral selective effects on other characters. Fisher’s theoretical arguments on the origin of genetic variation and Lewontin & Hub by ’s experiments show that such modifiers may exist. In Sheppard’s model, dominance evolves in a polymorphism maintained by disruptive or frequencydependent selection. If two different alleles produce two different mimetic forms, the hetero ¬ zygote and one of the homozygotes will be selected to give the optimum phenotype of one of the mimics and the other homozygote will be selected to give the optimum phenotype of the other one. In this model, the mimic which is the last to appear by mutation evolves dominance. Other small selective forces acting on the modifiers do not stop the evolution of dominance. Sheppard’s model should therefore be true in nature whether the modifiers are subject to other selective forces or not. A mathematical model demonstrated that a rare mimic would not evolve dominance if the modifier was maintained in the population by other selective forces producing a heterozygous advantage of more than 1%. Thus it follows from Clarke & S heppard’s discovery of certain rare mimics of Papilio dardanus that this is the greatest possible heterozygous advantage that can be acting on the modifiers.

scholarly journals Dominant TNF-α+ Mycobacterium tuberculosis–specific CD4+ T cell responses discriminate between latent infection and active disease

2011 ◽  
Vol 17 (3) ◽  
pp. 372-376 ◽  
Author(s):  
Alexandre Harari ◽  
Virginie Rozot ◽  
Felicitas Bellutti Enders ◽  
Matthieu Perreau ◽  
Jesica Mazza Stalder ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Latent Infection ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Tnf Α ◽  
Active Disease

scholarly journals Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

2016 ◽  
Author(s):  
Sean G. Byars ◽  
Qin Qin Huang ◽  
Lesley-Ann Gray ◽  
Samuli Ripatti ◽  
Gad Abraham ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Genetic Variation ◽  
Natural Selection ◽  
Coronary Artery ◽  
Positive Selection ◽  
Genetic Risk ◽  
Human Reproduction ◽  
Human Populations ◽  
Modern Humans ◽  
Artery Disease

AbstractTraditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. This suggests the presence of widespread antagonistic-pleiotropic tradeoffs on CAD loci, which provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.Author SummaryHow genetic variation contributes to disease is complex, especially for those such as coronary artery disease (CAD) that develop over the lifetime of individuals. One of the fundamental questions about CAD — whose progression begins in young adults with arterial plaque accumulation leading to life-threatening outcomes later in life — is why natural selection has not removed or reduced this costly disease. It is the leading cause of death worldwide and has been present in human populations for thousands of years, implying considerable pressures that natural selection should have operated on. Our study provides new evidence that genes underlying CAD have recently been modified by natural selection and that these same genes uniquely and extensively contribute to human reproduction, which suggests that natural selection may have maintained genetic variation contributing to CAD because of its beneficial effects on fitness. This study provides novel evidence that CAD has been maintained in modern humans as a byproduct of the fitness advantages those genes provide early in human lifecycles.

The Mycobacterial HBHA Protein: A Promising Biomarker for Tuberculosis

2019 ◽  
Vol 26 (11) ◽  
pp. 2051-2060 ◽  
Author(s):  
Flavio De Maio ◽  
Flavia Squeglia ◽  
Delia Goletti ◽  
Giovanni Delogu
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Surface Antigen ◽  
Disease Risk ◽  
Protein A ◽  
Heparin Binding ◽  
Major Goal ◽  
Latently Infected ◽  
Active Disease

A major goal in tuberculosis (TB) research is the identification, among the subjects infected with Mycobacterium tuberculosis (Mtb), of those with active TB, or at higher risk of developing active disease, from the latently infected subjects. The classical heterogeneity of Mtb infection and TB disease is a major obstacle toward the identification of reliable biomarkers that can stratify Mtb infected subjects based on disease risk. The heparin-binding haemagglutinin (HBHA) is a mycobacterial surface antigen that is implicated in tuberculosis (TB) pathogenesis. The host immune response against HBHA varies depending on the TB status and several studies are supporting the role of HBHA as a useful biomarker of TB.

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