Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction

Michelle A Favila; Nicholas S Geraci; Erliang Zeng; Brent Harker; David Condon; Rachel N Cotton; Asha Jayakumar; Vinita Tripathi; Mary Ann McDowell

doi:10.4049/jimmunol.1203230

Back

Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction

Journal article

Peer reviewed

Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction

Michelle A Favila, Nicholas S Geraci, Erliang Zeng, Brent Harker, David Condon, Rachel N Cotton, Asha Jayakumar, Vinita Tripathi and Mary Ann McDowell

The Journal of immunology (1950), Vol.192(12), pp.5863-5872

06/15/2014

DOI: 10.4049/jimmunol.1203230

PMCID: PMC4052223

PMID: 24808365

View Online

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.

Leishmania major - immunology

Leishmania donovani - immunology

Gene Expression Regulation - immunology

Dendritic Cells - immunology

Humans

Leishmaniasis, Cutaneous - pathology

Neoplasm Proteins - immunology

Dendritic Cells - pathology

Male

Interferon Regulatory Factor-7 - immunology

Leishmaniasis, Visceral - immunology

Interferon Type I - immunology

Leishmaniasis, Cutaneous - immunology

Signal Transduction - immunology

Female

Interleukin-12 Subunit p40 - immunology

Interferon Regulatory Factor-2 - immunology

Details

Title: Subtitle: Human dendritic cells exhibit a pronounced type I IFN signature following Leishmania major infection that is required for IL-12 induction
Creators: Michelle A Favila - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and
Nicholas S Geraci - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and
Erliang Zeng - Genomics and Bioinformatics Core Facility, University of Notre Dame, Notre Dame, IN 46556
Brent Harker - Genomics and Bioinformatics Core Facility, University of Notre Dame, Notre Dame, IN 46556
David Condon - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and
Rachel N Cotton - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and
Asha Jayakumar - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and
Vinita Tripathi - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and
Mary Ann McDowell - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556; and mcdowell.11@nd.edu
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.192(12), pp.5863-5872
DOI: 10.4049/jimmunol.1203230
PMID: 24808365
PMCID: PMC4052223
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R01AI056242 / NIAID NIH HHS T32GM075762 / NIGMS NIH HHS R01 AI056242 / NIAID NIH HHS K22 AI054343 / NIAID NIH HHS T32 GM075762 / NIGMS NIH HHS
Language: English
Date published: 06/15/2014
Academic Unit: Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Dental Research
Record Identifier: 9984065465902771

Metrics

24 Record Views

33 Times Cited - Web of Science