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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

A hypothetical model to explain virulent phenotype in leishmaniasis. The three groups of determinants are thought to interact with host immune system independently, but may progress sequentially to produce the spectrum of subclinical and clinical manifestions as the basis of virulent phenotypes seen.
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Figure 3: A hypothetical model to explain virulent phenotype in leishmaniasis. The three groups of determinants are thought to interact with host immune system independently, but may progress sequentially to produce the spectrum of subclinical and clinical manifestions as the basis of virulent phenotypes seen.

Mentions: Fig. 3 depicts schematically Leishmania invasive/evasive- and pathoantigenic determinants as different groups of parasite virulence-related molecules. Presumably, they interact sequentially with different compartments of the host immune system to cause leishmaniasis. The invasive/evasive determinants of Leishmania help them overcome the host immune and non-immune barriers to establish intracellular infection of macrophages. This infection by itself does not cause the disease, but it is a prerequisite for this state. Infection must be maintained in order for the transition from asymptomatic phase to symptomatic phase, especially when host immunity becomes down-regulated. The latter event alone produces no leishmaniasis without persistence of the infection. The invasive/evasive determinants are thus virulence factors in that sense, even though they contribute only indirectly to the virulent phenotype. During the subsequent chronic course of infection, it appears that some intracellular amastigotes are killed or lysed inadvertently due, perhaps, to the incomplete protection by their invasive/evasive determinants. As a result of this, some cytoplasmic molecules of amastigotes are exposed to the host immune system. The resulting immune response to these unique epitopes does not contribute to the anti-Leishmania immunity, but to the clinical symptoms observed in leishmaniasis. Thus, Leishmania determinants of infection and immunopathology are considered here as different, but sequentially necessary components for the expression of virulence.


Molecular determinants and regulation of Leishmania virulence.

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

A hypothetical model to explain virulent phenotype in leishmaniasis. The three groups of determinants are thought to interact with host immune system independently, but may progress sequentially to produce the spectrum of subclinical and clinical manifestions as the basis of virulent phenotypes seen.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: A hypothetical model to explain virulent phenotype in leishmaniasis. The three groups of determinants are thought to interact with host immune system independently, but may progress sequentially to produce the spectrum of subclinical and clinical manifestions as the basis of virulent phenotypes seen.
Mentions: Fig. 3 depicts schematically Leishmania invasive/evasive- and pathoantigenic determinants as different groups of parasite virulence-related molecules. Presumably, they interact sequentially with different compartments of the host immune system to cause leishmaniasis. The invasive/evasive determinants of Leishmania help them overcome the host immune and non-immune barriers to establish intracellular infection of macrophages. This infection by itself does not cause the disease, but it is a prerequisite for this state. Infection must be maintained in order for the transition from asymptomatic phase to symptomatic phase, especially when host immunity becomes down-regulated. The latter event alone produces no leishmaniasis without persistence of the infection. The invasive/evasive determinants are thus virulence factors in that sense, even though they contribute only indirectly to the virulent phenotype. During the subsequent chronic course of infection, it appears that some intracellular amastigotes are killed or lysed inadvertently due, perhaps, to the incomplete protection by their invasive/evasive determinants. As a result of this, some cytoplasmic molecules of amastigotes are exposed to the host immune system. The resulting immune response to these unique epitopes does not contribute to the anti-Leishmania immunity, but to the clinical symptoms observed in leishmaniasis. Thus, Leishmania determinants of infection and immunopathology are considered here as different, but sequentially necessary components for the expression of virulence.

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