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SerpinB2 deficiency modulates Th1⁄Th2 responses after schistosome infection

W A Schroder1, J Gardner, T T Le

  • 1Queensland Institute of Medical Research, Brisbane, Qld., Australia.

Parasite Immunology
|November 20, 2010
PubMed

Insights

SerpinB2 deficiency in mice reduced fibrosis during Schistosoma japonicum infection and altered immune responses. These findings suggest SerpinB2 influences Th1/Th2 balance in parasitic infections.

Area of Science:

  • Immunology
  • Parasitology
  • Molecular Biology

Background:

  • SerpinB2 (plasminogen activator inhibitor type-2) is macrophage-produced and infection-upregulated.
  • Its in vivo role in inhibiting urokinase plasminogen activator is not well-established.
  • Previous studies indicated SerpinB2 knockout mice exhibit enhanced Th1 responses.

Purpose of the Study:

  • To investigate the role of SerpinB2 in Schistosoma japonicum infection.
  • To determine the impact of SerpinB2 deficiency on granuloma formation, fibrosis, and immune cell responses.
  • To assess the effect of SerpinB2 deficiency on Th1 and Th2 immune polarization.

Main Methods:

  • Utilized SerpinB2 knockout (SerpinB2-/-) and wild-type (WT) mice.
  • Induced Schistosoma japonicum infection and immunized with soluble egg antigen (SEA).
  • Quantified parasite burden, granuloma characteristics, fibrosis (Sirius red staining), and gene expression (iNOS, IL-6, IL-10, TNFa, Arg 1, IL-13).
  • Measured SEA-specific IgG1 antibody levels.

Main Results:

  • Schistosoma japonicum infection significantly upregulated hepatic SerpinB2 mRNA in WT mice.
  • SerpinB2-/- mice showed unaffected worm/egg burden and granuloma size but reduced fibrosis.
  • Granulomas in SerpinB2-/- mice exhibited increased iNOS, IL-6, IL-10, TNFa, and decreased Arg 1, IL-13 mRNA.
  • SEA immunization in SerpinB2-/- mice led to reduced SEA-specific IgG1 levels.

Conclusions:

  • SerpinB2 deficiency does not impact parasite burden or granuloma size in Schistosoma japonicum infection.
  • SerpinB2 deficiency is associated with reduced liver fibrosis and a shift towards Th1-biased immune responses.
  • These findings highlight SerpinB2's role in modulating immune polarization and fibrotic processes during parasitic infections.

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