PD-L2 negatively regulates Th1-mediated immunopathology during Fasciola hepatica infection
| Autor: | Maria del Pilar Aoki, Cinthia C. Stempin, Fabio M. Cerbán, Laura Cervi, Cristian Roberto Falcón, Claudia Cristina Motran |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Cell Plasticity Ciencias de la Salud Gene Knockout Techniques Mice 0302 clinical medicine Immunopathology Pd-L2 Macrophage Cells Cultured biology F. Hepatica F. hepatica Interleukin-10 Otras Ciencias de la Salud Cytokine Oncology Th1 response Macrophagemacrophage purl.org/becyt/ford/3 [https] medicine.symptom Th1 Response Research Paper Fascioliasis CIENCIAS MÉDICAS Y DE LA SALUD PD-L2 Inflammation macrophage 03 medical and health sciences purl.org/becyt/ford/3.3 [https] Interferon-gamma Immune system Hepatica parasitic diseases Splenocyte medicine Fasciola hepatica Animals Humans Arginase Th1 Cells biology.organism_classification Programmed Cell Death 1 Ligand 2 Protein Molecular biology infection 030104 developmental biology Immunology Macrophages Peritoneal 030215 immunology |
| Zdroj: | Oncotarget CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | Macrophage plasticity is critical for controlling inflammation including thoseproduced by helminth infections, where alternatively activated macrophages (AAM)are accumulated in tissues. AAM expressing the co-inhibitory molecule programmeddeath ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasiticinfections. However, the role of PD-L2 during F. hepatica infection has not yet beenexplored. We observed that F. hepatica infection or a F. hepatica total extract (TE)injection increased the expression of PD-L2 on peritoneal macrophages. In addition,the absence of PD-L2 expression correlated with an increase in susceptibility to F.hepatica infection, as evidenced by the shorter survival and increased liver damageobserved in PD-L2 deficient (KO) mice. We assessed the contribution of the PD-L2pathway to Th2 polarization during this infection, and found that the absence of PD-L2caused a diminished Th2 type cytokine production by TE stimulated splenocytes fromPD-L2 KO infected compared with WT mice. Besides, splenocytes and intrahepaticleukocytes from infected PD-L2 KO mice showed higher levels of IFN-γ than thosefrom WT mice. Arginase expression and activity and IL-10 production were reducedin macrophages from PD-L2 KO mice compared to those from WT mice, revealing astrong correlation between PD-L2 expression and AAM polarization. Taken together,our data indicate that PD-L2 expression in macrophages is critical for AAM inductionand the maintenance of an optimal balance between the Th1- and Th2-type immuneresponses to assure host survival during F. hepatica infection. Fil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Motran, Claudia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Falcón, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina |
| Databáze: | OpenAIRE |
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