PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis.
Eur J Immunol
; 36(1): 58-64, 2006 Jan.
Article
en En
| MEDLINE
| ID: mdl-16358363
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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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
2_enfermedades_transmissibles
/
4_leishmaniasis
/
6_skin_diseases
Asunto principal:
Péptidos
/
Glicoproteínas de Membrana
/
Leishmaniasis Cutánea
/
Antígeno B7-1
/
Células Th2
/
Células TH1
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos