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Published on: July 28, 2010
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.
Abstract:
Follicular dendritic cells (FDCs) play a pivotal role in the germinal center (GC) response and in the development and regulation of B lymphocytes. Pathologic changes in GCs and a loss of FDCs have previously been noted in various viral infections, notably HIV-1. However, such changes have not been formally described in a chronic parasitic infection. In BALB/c mice infected with Leishmania donovani, parasites persist in the spleen for long periods, with associated splenomegaly. To examine the fate of FDC during the course of this chronic infection, we used 1) immunohistology, with FDC-specific mAbs; and 2) passive immunization with immune complexes, followed by light and electron microscopy. This study demonstrates that destruction of FDCs and a concomitant loss of GCs are associated with chronic visceral leishmaniasis. These pathologic effects are notable from 4 wk postinfection. At 8 wk postinfection and beyond, FDC are almost undetectable by both immunohistology and functional immune complex trapping. The loss of FDCs is associated with the infiltration of heavily parasitized macrophages into the GC, and reduction in parasite burden by chemotherapy is able to retard the process of FDC destruction. These data directly demonstrate for the first time the loss of FDCs during a chronic parasite infection and suggest a mechanism underlying the aberrant regulation of B cell function in murine visceral leishmaniasis.
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