| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Zeng, Erliang Condon, David Tripathi, Vinita Harker, Brent Cotton, Rachel N. Favila, Michelle A. Jayakumar, Asha Geraci, Nicholas S. McDowell, Mary Ann |
| Description |
Author Affiliation: Favila MA ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556); Geraci NS ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556); Zeng E ( Genomics and Bioinformatics Core Facility, University of Notre Dame, Notre Dame, IN 46556.); Harker B ( Genomics and Bioinformatics Core Facility, University of Notre Dame, Notre Dame, IN 46556.); Condon D ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556); Cotton RN ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556); Jayakumar A ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556); Tripathi V ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556); McDowell MA ( Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556) |
| Abstract |
Leishmania major-infected human dendritic cells (DCs) exhibit a marked induction of IL-12, ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. The host cell transcription machinery associated with the specific IL-12 induction observed during L. major infection remains to be thoroughly elucidated. In this study, we used Affymetrix GeneChip (Affymetrix) to globally assess the host cell genes and pathways associated with early L. major infection in human myeloid-derived DCs. Our data revealed 728 genes were significantly differentially expressed and molecular signaling pathway revealed that the type I IFN pathway was significantly enriched. Addition of a neutralizing type I IFN decoy receptor blocked the expression of IRF7 and IL-12p40 during DC infection, indicating the L. major-induced expression of IL-12p40 is dependent upon the type I IFN signaling pathway. In stark contrast, IL-12p40 expression is not elicited by L. donovani, the etiological agent of deadly visceral leishmaniasis. Therefore, we examined the gene expression profile for several IFN response genes in L. major versus L. donovani DC infections. Our data revealed that L. major, but not L. donovani, induces expression of IRF2, IRF7, and IFIT5, implicating the regulation of type I IFN-associated signaling pathways as mediating factors toward the production of IL-12. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1203230 |
| Journal |
The Journal of Immunology |
| Issue Number |
12 |
| Volume Number |
192 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-06-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Dendritic Cells Immunology Gene Expression Regulation Interferon Type I Interleukin-12 Subunit P40 Leishmania Major Leishmaniasis, Cutaneous Pathology Interferon Regulatory Factor-2 Interferon Regulatory Factor-7 Leishmania Donovani Leishmaniasis, Visceral Neoplasm Proteins Signal Transduction Research Support, N.i.h., Extramural Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
