Destruction of follicular dendritic cells during chronic visceral leishmaniasis

S C Smelt1, C R Engwerda, M McCrossen

  • 1Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, United Kingdom.

Insights

Chronic parasitic infection with Leishmania donovani causes the destruction of follicular dendritic cells (FDCs) and germinal centers in mice. This loss of FDCs is linked to parasite burden and impacts B lymphocyte regulation.

Area of Science:

  • Immunology
  • Parasitology
  • Cell Biology

Background:

  • Follicular dendritic cells (FDCs) are crucial for germinal center (GC) responses and B lymphocyte regulation.
  • FDC loss and GC pathology are known in viral infections like HIV-1, but not well-described in chronic parasitic infections.
  • Visceral leishmaniasis is a chronic parasitic infection characterized by persistent spleen parasites and splenomegaly.

Purpose of the Study:

  • To investigate the fate of FDCs during chronic Leishmania donovani infection in mice.
  • To determine if FDC destruction and GC loss occur in this parasitic model.
  • To explore the relationship between parasite burden, FDC loss, and B cell function.

Main Methods:

  • Immunohistology using FDC-specific monoclonal antibodies (mAbs).
  • Passive immunization with immune complexes followed by light and electron microscopy.
  • Assessment of FDC presence and GC structure at various time points post-infection.

Main Results:

  • Chronic Leishmania donovani infection leads to the destruction of FDCs and loss of GCs, evident from 4 weeks post-infection.
  • FDCs become nearly undetectable by 8 weeks post-infection using immunohistology and immune complex trapping.
  • Parasitized macrophages infiltrate GCs, and chemotherapy reduces FDC destruction, indicating a link to parasite burden.

Conclusions:

  • This study provides the first direct evidence of FDC loss during chronic parasitic infection.
  • The findings suggest a mechanism for aberrant B cell regulation in murine visceral leishmaniasis due to FDC destruction.
  • FDC loss is associated with parasite infiltration and can be partially mitigated by reducing parasite burden.

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