Leishmania model for microbial virulence: The relevance of parasite multiplication and pathoantigenicity

Kwang Poo Chang, Steven G. Reed, Bradford S. McGwire, Lynn Soong

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Leishmanial mechanisms of virulence have been proposed previously to involve two different groups of parasite molecules. One group consists of largely surface and secretory products, and the second group includes intracellular molecules, referred to as 'pathoantigens'. In the first group are invasive/evasive determinants, which protect not only parasites themselves, but also infected host cells from premature cytolysis. These determinants help intracellular amastigotes maintain continuous infection by growing at a slow rate in the parasitophorous vacuoles of host macrophages. This is illustrated in closed in vitro systems, e.g. Leishmania amazonensis in macrophage cell lines. Although individual macrophages may become heavily parasitized at times, massive destruction of macrophages has not been observed to result from uncontrolled parasite replication. This is thus unlikely to be the direct cause of virulence manifested as the clinical symptoms seen in human leishmaniasis. Of relevance is likely the second group of immunopathology-causing parasite 'pathoantigens'. These are highly conserved cytoplasmic proteins, which have been found to contain Leishmania-unique epitopes immunologically active in leishmaniasis. How these intracellular parasite antigens become exposed to the host immune system is accounted for by periodic cytolysis of the parasites during natural infection. This event is notable with a small number of parasites, even as they grow in an infected culture. The cytolysis of these parasites to release 'pathoantigens' may be inadvertent or medicated by specific mechanisms. Information on the pathoantigenic epitopes is limited. T-cell epitopes have long been recognized, albeit ill-defined, as important in eliciting CD4+ cell development along either the Th1 or Th2 pathway. Their operational mechanisms in suppressing or exacerbating cutaneous disease are still under intensive investigation. However, immune response to B-cell epitopes of such 'pathoantigens' is clearly futile and counterproductive. Their intracellular location within the parasites renders them inaccessible to the specific antibodies generated. One example is the Leishmania K39 epitope, against which antibodies are produced in exceedingly high titers, especially in Indian kala-azar. Here, we consider the hypothetical emergence of this pathoantigenicity and its potential contributions to the virulent phenotype in the form of immunopathology. Microbial virulence may be similarly explained in other emerging and re-emerging infectious diseases. Attenuation of microbial virulence may be achieved by genetic elimination of pathoantigenicity, thereby providing mutants potentially useful as avirulent live vaccines for immunoprophylasis of infectious diseases.

Original languageEnglish (US)
Pages (from-to)375-390
Number of pages16
JournalActa Tropica
Volume85
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Leishmania
Virulence
Parasites
virulence
parasites
epitopes
cytolysis
macrophages
Macrophages
immunopathology
Epitopes
Leishmaniasis
leishmaniasis
Leishmania amazonensis
Emerging Communicable Diseases
B-Lymphocyte Epitopes
amastigotes
antibodies
visceral leishmaniasis
T-Lymphocyte Epitopes

Keywords

  • Infection
  • Leishmania
  • Leishmaniasis
  • Live vaccine
  • Macrophage
  • Microbial virulence
  • Pathoantigenicity

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Leishmania model for microbial virulence : The relevance of parasite multiplication and pathoantigenicity. / Chang, Kwang Poo; Reed, Steven G.; McGwire, Bradford S.; Soong, Lynn.

In: Acta Tropica, Vol. 85, No. 3, 01.03.2003, p. 375-390.

Research output: Contribution to journalArticle

Chang, Kwang Poo ; Reed, Steven G. ; McGwire, Bradford S. ; Soong, Lynn. / Leishmania model for microbial virulence : The relevance of parasite multiplication and pathoantigenicity. In: Acta Tropica. 2003 ; Vol. 85, No. 3. pp. 375-390.
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