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Molecular determinants and regulation of Leishmania virulence.

Chang KP, McGwire BS - Kinetoplastid Biol Dis (2002)

Bottom Line: The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment.Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure.The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology/Immunology, University of Health Sciences/Chicago Medical School, North Chicago, IL, USA. changk@finchcms.edu

ABSTRACT
A Leishmania model to explain microbial virulence in chronic infectious diseases is proposed. All these diseases progress from infection to symptomatic phase to host death or recovery. The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment. The first group consists of invasive/evasive determinants, which are largely parasite cell surface and secreted molecules. Their activities help parasites establish infection by overcoming host immunologic and non-immunologic barriers. These determinants do not cause disease per se, but are indispensable for infection necessary for the development of a disease-state. The second group of parasite molecules consists of "pathoantigenic" determinants - unique parasite epitopes present often within otherwise highly conserved cytoplasmic molecules. Immune response against these determinants is thought to result in immunopathology manifested as clinical signs or symptoms, namely the virulent phenotype. The third group of parasite molecules is hypothetically perceived as vaccine determinants. Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure. Differential expression of these determinants alone by parasites may alter their interactions with the hosts. Virulent phenotype is consequently presented as a spectrum of manifestations from asymptomatic infection to fatality. A secondary level of regulation lies in host genetic and environmental factors. The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases.

No MeSH data available.


Related in: MedlinePlus

Regulation of Leishmania virulence at genetic levels. Blue, Green and Yellow squares with "+", Positive contributors for the multiple determinants discussed; pink square with "-", negative contributors coding for products, which reduce virulence; Red square blank, Facultative contributors, which do not contribute to virulence under the normal conditions.
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Figure 4: Regulation of Leishmania virulence at genetic levels. Blue, Green and Yellow squares with "+", Positive contributors for the multiple determinants discussed; pink square with "-", negative contributors coding for products, which reduce virulence; Red square blank, Facultative contributors, which do not contribute to virulence under the normal conditions.

Mentions: Fig. 4 considers Leishmania virulence at the gene level based on hypothetical grounds and on some gene knockout experimental data in the literature. There appear to be three functional groups of genes involved: (A) Positive contributors for the multiple determinants already discussed (Fig. 4., Blue, Green and Yellow squares with "+"); (B) negative contributors (pink square with "-") coding for products, which reduce virulence; and (C) facultative contributors (Red square blank), which normally do not participate in virulence, but do so in the absence of a positive contributor. Normally, the virulent phenotype seen in a given condition represents a balanced presence of positive and negative genes with no involvement of the facultative ones (Fig. 4, 1st row, double-headed horizontal arrow). When one of the positive genes is silenced or lost, virulence may decrease, as expected (Fig. 4, 2nd row, downward arrow). Alternatively, it may remain unchanged when the gene of concern is functionally "backed up" or replaced with another positive contributor via up-regulation of its expression (Fig. 4, 3rd Row, duplication of the green squares with "++") or with that of a facultative gene (Fig. 4, 4th row, red square with "+"). This scenario may explain the experimental findings that knockouts of "virulence genes" do not always result in changes in the phenotype expected. Silencing or loss of the negative gene is accompanied by an increase in virulence (Fig. 4, 6th Row, upward arrow). There is at least one example in the literature for the presence of negative genes [22].


Molecular determinants and regulation of Leishmania virulence.

Chang KP, McGwire BS - Kinetoplastid Biol Dis (2002)

Regulation of Leishmania virulence at genetic levels. Blue, Green and Yellow squares with "+", Positive contributors for the multiple determinants discussed; pink square with "-", negative contributors coding for products, which reduce virulence; Red square blank, Facultative contributors, which do not contribute to virulence under the normal conditions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC119322&req=5

Figure 4: Regulation of Leishmania virulence at genetic levels. Blue, Green and Yellow squares with "+", Positive contributors for the multiple determinants discussed; pink square with "-", negative contributors coding for products, which reduce virulence; Red square blank, Facultative contributors, which do not contribute to virulence under the normal conditions.
Mentions: Fig. 4 considers Leishmania virulence at the gene level based on hypothetical grounds and on some gene knockout experimental data in the literature. There appear to be three functional groups of genes involved: (A) Positive contributors for the multiple determinants already discussed (Fig. 4., Blue, Green and Yellow squares with "+"); (B) negative contributors (pink square with "-") coding for products, which reduce virulence; and (C) facultative contributors (Red square blank), which normally do not participate in virulence, but do so in the absence of a positive contributor. Normally, the virulent phenotype seen in a given condition represents a balanced presence of positive and negative genes with no involvement of the facultative ones (Fig. 4, 1st row, double-headed horizontal arrow). When one of the positive genes is silenced or lost, virulence may decrease, as expected (Fig. 4, 2nd row, downward arrow). Alternatively, it may remain unchanged when the gene of concern is functionally "backed up" or replaced with another positive contributor via up-regulation of its expression (Fig. 4, 3rd Row, duplication of the green squares with "++") or with that of a facultative gene (Fig. 4, 4th row, red square with "+"). This scenario may explain the experimental findings that knockouts of "virulence genes" do not always result in changes in the phenotype expected. Silencing or loss of the negative gene is accompanied by an increase in virulence (Fig. 4, 6th Row, upward arrow). There is at least one example in the literature for the presence of negative genes [22].

Bottom Line: The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment.Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure.The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology/Immunology, University of Health Sciences/Chicago Medical School, North Chicago, IL, USA. changk@finchcms.edu

ABSTRACT
A Leishmania model to explain microbial virulence in chronic infectious diseases is proposed. All these diseases progress from infection to symptomatic phase to host death or recovery. The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment. The first group consists of invasive/evasive determinants, which are largely parasite cell surface and secreted molecules. Their activities help parasites establish infection by overcoming host immunologic and non-immunologic barriers. These determinants do not cause disease per se, but are indispensable for infection necessary for the development of a disease-state. The second group of parasite molecules consists of "pathoantigenic" determinants - unique parasite epitopes present often within otherwise highly conserved cytoplasmic molecules. Immune response against these determinants is thought to result in immunopathology manifested as clinical signs or symptoms, namely the virulent phenotype. The third group of parasite molecules is hypothetically perceived as vaccine determinants. Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure. Differential expression of these determinants alone by parasites may alter their interactions with the hosts. Virulent phenotype is consequently presented as a spectrum of manifestations from asymptomatic infection to fatality. A secondary level of regulation lies in host genetic and environmental factors. The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases.

No MeSH data available.


Related in: MedlinePlus