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Fibroblasts as host cells in latent leishmaniosis
C Bogdan1, N Donhauser, R Döring
1Institute of Clinical Microbiology, Department of Anatomy, University of Erlangen, D-91054 Erlangen, Germany. christian.bogdan@mikrobio.med.uni-erlangen.de
Abstract:
Intracellular parasites are known to persist lifelong in mammalian hosts after the clinical cure of the disease, but the mechanisms of persistence are poorly understood. Here, we show by confocal laser microscopy that in the draining lymph nodes of mice that had healed a cutaneous infection with Leishmania major, 40% of the persisting parasites were associated with fibroblasts forming the reticular meshwork of the lymph nodes. In vitro, both promastigotes and amastigotes of L. major infected primary skin or lymph node fibroblasts. Compared with macrophages, cytokine-activated fibroblasts had a reduced ability to express type 2 nitric oxide synthase and to kill intracellular L. major. These data identify fibroblasts as an important host cell for Leishmania during the chronic phase of infection and suggest that they might serve as safe targets for the parasites in clinically latent disease.
Insights
Fibroblasts, not just macrophages, harbor Leishmania parasites in mice long after infection. These fibroblasts are less effective at killing the parasites, suggesting a role in chronic Leishmania infections.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Intracellular parasites like Leishmania major can persist lifelong in mammalian hosts, even after clinical cure.
- The precise mechanisms enabling long-term parasite persistence remain poorly understood.
- Identifying host cells involved in chronic infection is crucial for understanding latent disease.
Purpose of the Study:
- To investigate the cellular mechanisms of Leishmania major parasite persistence in mammalian hosts.
- To identify potential host cells harboring parasites during the chronic phase of infection.
- To compare the parasite-killing capabilities of different host cell types.
Main Methods:
- Confocal laser microscopy was used to visualize parasite localization in draining lymph nodes of infected mice.
- In vitro infection models utilized primary skin and lymph node fibroblasts with Leishmania major promastigotes and amastigotes.
- Cytokine-activated fibroblasts and macrophages were assessed for nitric oxide synthase expression and parasite killing ability.
Main Results:
- Confocal microscopy revealed that 40% of persisting Leishmania major parasites in healed murine infections were associated with lymph node fibroblasts.
- Both promastigote and amastigote forms of Leishmania major successfully infected primary fibroblasts in vitro.
- Cytokine-activated fibroblasts demonstrated reduced expression of type 2 nitric oxide synthase and impaired killing of intracellular Leishmania compared to macrophages.
Conclusions:
- Fibroblasts are identified as a significant host cell reservoir for Leishmania during the chronic phase of infection.
- Fibroblasts may act as protected niches for Leishmania parasites, contributing to clinically latent disease.
- Understanding fibroblast-parasite interactions is key to developing strategies against persistent parasitic infections.