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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

Some invasive/evasive determinants of Leishmania proposed to play important roles in their infection of mammalian hosts.
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Figure 1: Some invasive/evasive determinants of Leishmania proposed to play important roles in their infection of mammalian hosts.

Mentions: These determinants include most, if not all Leishmania molecules that have been studied as "virulence factors" in the literature (see Fig. 1). All these molecules appear to play certain roles in Leishmania infection of macrophages [1]. They are referred to here as invasive/evasive determinants because they help Leishmania successfully establish intracellular parasitism in the following sequential events: (A) evasion of humoral lytic factors; (B) attachment of parasites to macrophages followed by their intracellular entry into these phagocytes; (C) the intracellular survival of the endocytized parasites; (D) promastigote-to-amastigote differentiation; and (E) replication of the amastigotes. The categorization of the host-parasite cellular interactions into sequential events pertains to the primary infection of macrophages in the mammalian hosts by promastigotes. Events (A) – (C) and (E) are relevant as well to the secondary infection of macrophages by amastigotes from already infected cells. The spreading of amastigotes to infect additional cells must be considered as crucial for the development of leishmaniasis. However, it may be mechanistically a rather simple event in considering normal functions of macrophages. One of their functions is to scavenge damaged or dying cells and their cellular debris, which may include degenerating cells (due to heavy parasitization), parasitophorous vacuoles and even released amastigotes with adherent host molecules in leishmaniasis.


Molecular determinants and regulation of Leishmania virulence.

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

Some invasive/evasive determinants of Leishmania proposed to play important roles in their infection of mammalian hosts.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Some invasive/evasive determinants of Leishmania proposed to play important roles in their infection of mammalian hosts.
Mentions: These determinants include most, if not all Leishmania molecules that have been studied as "virulence factors" in the literature (see Fig. 1). All these molecules appear to play certain roles in Leishmania infection of macrophages [1]. They are referred to here as invasive/evasive determinants because they help Leishmania successfully establish intracellular parasitism in the following sequential events: (A) evasion of humoral lytic factors; (B) attachment of parasites to macrophages followed by their intracellular entry into these phagocytes; (C) the intracellular survival of the endocytized parasites; (D) promastigote-to-amastigote differentiation; and (E) replication of the amastigotes. The categorization of the host-parasite cellular interactions into sequential events pertains to the primary infection of macrophages in the mammalian hosts by promastigotes. Events (A) – (C) and (E) are relevant as well to the secondary infection of macrophages by amastigotes from already infected cells. The spreading of amastigotes to infect additional cells must be considered as crucial for the development of leishmaniasis. However, it may be mechanistically a rather simple event in considering normal functions of macrophages. One of their functions is to scavenge damaged or dying cells and their cellular debris, which may include degenerating cells (due to heavy parasitization), parasitophorous vacuoles and even released amastigotes with adherent host molecules in leishmaniasis.

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