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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 27, 2010
Impact of Leishmania mexicana infection on dendritic cell signaling and functions
Irazú Contreras1, José A Estrada1, Hannah Guak2
1Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada; Neurochemistry Laboratory, Faculty of Medicine. Universidad Autónoma del Estado de México, Toluca, Estado de México, México.
Abstract:
Leishmania parasites have the ability to modify macrophage signaling pathways in order to survive and multiply within its mammalian host. They are also known to invade other cells including neutrophils, fibroblasts and dendritic cells (DCs). DCs have an important role in immunity as the link between innate and adaptive immunity, necessary for the development of an effective response; however, the impact of Leishmania mexicana infection on DCs has been poorly studied. Herein, we report that Leishmania infection rapidly induced DC protein tyrosine phosphatases activity, leading to MAP kinases inactivation. In line with this, L. mexicana was found to decrease the nuclear translocation of transcription factors such as AP-1 and NF-κB. Concomitantly, L. mexicana-infected DCs showed reduced expression of several surface antigen-presenting and co-stimulatory molecules upon LPS stimulation. Leishmania-induced interference on DC maturation was further reflected by their reduced capacity to present OVA antigen to OVA-specific T cells, as shown by abrogation of IL-2 production by the T cells. Collectively, our data revealed that DC infection by L. mexicana appears to affect the cellular and immunological mechanisms necessary for the development of an effective and protective immune response, therefore favouring the survival and propagation of the parasite within its host.
Insights
Leishmania mexicana infection impairs dendritic cell (DC) function by disrupting signaling pathways, reducing their ability to initiate adaptive immunity. This parasite manipulation aids Leishmania survival and spread within the host.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Leishmania parasites manipulate host macrophage signaling for survival.
- Dendritic cells (DCs) are crucial for linking innate and adaptive immunity.
- The impact of Leishmania mexicana on DC function remains understudied.
Purpose of the Study:
- To investigate the effects of Leishmania mexicana infection on dendritic cell (DC) function and immune signaling.
- To elucidate the mechanisms by which Leishmania mexicana interferes with DC maturation and antigen presentation.
Main Methods:
- Assessed protein tyrosine phosphatases activity in infected DCs.
- Measured MAP kinases inactivation and transcription factor nuclear translocation (AP-1, NF-κB).
- Analyzed surface molecule expression, antigen presentation capacity, and T cell activation (IL-2 production).
Main Results:
- Leishmania infection rapidly increased DC protein tyrosine phosphatases activity, inactivating MAP kinases.
- L. mexicana reduced nuclear translocation of AP-1 and NF-κB transcription factors.
- Infected DCs exhibited decreased surface molecule expression and impaired antigen presentation, leading to reduced T cell IL-2 production.
Conclusions:
- Leishmania mexicana infection disrupts DC maturation and function, compromising their ability to initiate protective immune responses.
- The parasite's interference with DC signaling and antigen presentation facilitates its survival and propagation within the host.
- Understanding these mechanisms is vital for developing strategies against Leishmania infections.
