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Published on: July 27, 2010
The role of mannose receptor during experimental leishmaniasis
Oleg E Akilov1, Rachel E Kasuboski, Cristina R Carter
1Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, 215 Galvin Life Sciences, Notre Dame, IN 46556, USA.
Abstract:
The primary host cells for Leishmania replication are macrophages (MP). Several molecules on the surface of professional phagocytic cells have been implicated in the initial process of parasite internalization and initiation of signaling pathways. These pattern recognition receptors distinguish molecular patterns on pathogen surfaces. Mannose receptor (MR), specifically, recognizes mannose residues on the surface of Leishmania parasites. We studied the role of MR in the pathogenesis of experimental cutaneous and visceral leishmaniasis using MR-deficient [MR-knockout (KO)] C57BL/6 mice. MR-deficient MP exhibited a comparable infection rate and cytokine production. In the absence of MR, the clinical course of Leishmania major and Leishmania donovani infections was similar in MR-KO and wild-type mice (MR-WT). Furthermore, immunohistochemistry of cutaneous lesions from MR-KO and MR-WT mice revealed no differences in lesion architecture or cell components. Inhibition of MP responses is a hallmark of Leishmania infection; our data demonstrate further that host MR is not essential for blocking IFN-gamma/LPS-induced IL-12 production and MAPK activation by Leishmania. Thus, we conclude that the MR is not essential for host defense against Leishmania infection or regulation of IL-12 production.
Insights
The mannose receptor (MR) does not play an essential role in Leishmania parasite infection or host defense. Studies using MR-knockout mice showed no significant differences in infection rates or disease progression, indicating MR is not critical for Leishmania pathogenesis.
Area of Science:
- Immunology
- Parasitology
- Infectious Diseases
Background:
- Macrophages (MP) are primary host cells for Leishmania replication.
- Pattern recognition receptors mediate parasite internalization and signaling.
- Mannose receptor (MR) recognizes mannose residues on Leishmania surfaces.
Purpose of the Study:
- To investigate the role of MR in experimental cutaneous and visceral leishmaniasis.
- To determine if MR is essential for Leishmania infection and host defense.
Main Methods:
- Utilized MR-deficient (MR-knockout) and wild-type C57BL/6 mice.
- Assessed parasite infection rates and cytokine production in macrophages.
- Analyzed clinical course of Leishmania infections (L. major, L. donovani).
- Performed immunohistochemistry on cutaneous lesions.
Main Results:
- MR-deficient macrophages showed comparable infection rates and cytokine production.
- MR-knockout and wild-type mice exhibited similar clinical courses for both L. major and L. donovani infections.
- No differences in lesion architecture or cellular components were observed between MR-KO and MR-WT mice.
- Host MR was not essential for blocking IFN-gamma/LPS-induced IL-12 production and MAPK activation.
Conclusions:
- The mannose receptor (MR) is not essential for host defense against Leishmania infection.
- MR does not play a critical role in regulating IL-12 production during Leishmania infection.
- These findings suggest alternative pathways are involved in Leishmania pathogenesis and host immune response.
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