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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 28, 2010
PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis
Spencer C Liang1, Rebecca J Greenwald, Yvette E Latchman
1Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Insights
Programmed death 1 ligand 1 (PD-L1) and PD-L2 have distinct roles in Leishmania infection immunity. PD-L1 deficiency enhances resistance, while PD-L2 deficiency exacerbates disease.
Area of Science:
- Immunology
- Infectious Diseases
- Molecular Biology
Background:
- Programmed death 1 (PD-1) pathway plays a crucial role in immune regulation.
- PD-1 ligands, PD-L1 and PD-L2, are involved in T cell responses.
- Their specific roles in host defense against parasitic infections remain incompletely understood.
Purpose of the Study:
- To compare the distinct roles of PD-L1 and PD-L2 in regulating immunity to Leishmania mexicana infection.
- To elucidate the impact of PD-L1 and PD-L2 deficiency on host immune responses and disease outcomes.
Main Methods:
- Utilized knockout mouse models (PD-L1(-/-) and PD-L2(-/-)) to study Leishmania mexicana infection.
- Assessed disease progression, parasite burden, and host immune cell responses (Th1/Th2 cytokines, antibody production).
Main Results:
- PD-L1(-/-) mice exhibited resistance to L. mexicana, characterized by reduced lesion growth and parasite load.
- PD-L2(-/-) mice showed exacerbated disease with increased parasite burden.
- PD-L1 deficiency led to reduced IL-4 production, indicating impaired Th2 differentiation and contributing to resistance.
- PD-L2 deficiency resulted in increased Leishmania-specific IgG production, potentially suppressing healing.
Conclusions:
- PD-L1 and PD-L2 exert distinct and opposing effects on the immune response to Leishmania mexicana.
- PD-L1 contributes to regulating Th cell differentiation and host resistance.
- PD-L2 influences antibody production and disease severity, suggesting complex immune modulation roles.
Abstract:
To compare the roles of programmed death 1 ligand 1 (PD-L1) and PD-L2 in regulating immunity to infection, we investigated responses of mice lacking PD-L1 or PD-L2 to infection with Leishmania mexicana. PD-L1(-/-) and PD-L2(-/-) mice exhibited distinct disease outcomes following infection with L. mexicana. In comparison to susceptible WT mice, PD-L1(-/-) mice showed resistance to L. mexicana, as demonstrated by reduced growth of cutaneous lesions and parasite burden. In contrast, PD-L2(-/-) mice developed exacerbated disease with increased parasite burden. Host resistance to L. mexicana is partly associated with the development of a Th1 response and down-regulation of the Th2 response. Both PD-L1(-/-) and PD-L2(-/-) mice produced levels of IFN-gamma similar to WT mice. However, the development of IL-4-producing cells was reduced in PD-L1(-/-) mice, demonstrating a role for PD-L1 in regulating Th cell differentiation. This inadequate Th2 response may explain the increased resistance of PD-L1(-/-) mice. Although no alterations in Th1/Th2 skewing were observed in PD-L2(-/-) mice, PD-L2(-/-) mice exhibited a marked increase in L. mexicana-specific antibody production. Increased Leishmania-specific IgG production may suppress the healing response through FcgammaR ligation on macrophages. Taken together, our results demonstrate that PD-L1 and PD-L2 have distinct roles in regulating the immune response to L. mexicana.
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