Immunomodulation of dual specificity phosphatase 4 during visceral leishmaniasis.

Abstract

DUSP4, an inducible protein has a substrate specificity toward ERK1/2, a component of MAP kinase which is enhanced during Leishmania infection. The DUSP4-/- mice show increased susceptibility towards the infection caused by Toxoplasma gondii and Leishmania mexicana. These observations emphatically established the fact that unlike DUSP1, DUSP4 has host protective role. In our study, it has been Leishmania donovani, the causative agent of visceral leishmaniasis (VL) significantly reduced the expression of DUSP4 during infection. In order to find out the host protective role of DUSP4 in macrophages during VL, we silenced DUSP4 prior to infection and the parasite number within macrophage was counted. Under DUSP4 knock-down condition, phosphorylation of p38 MAPK and generation of pro-inflammatory response like IL-12, TNF-α, and iNOS was decreased significantly. Silencing DUSP4 promoted the phosphorylation of ERK1/2 and the generation of anti-inflammatory response like- IL-10, TGF-β with increased Arginase-1 and Cox-2 activity. Glycyrrhizic Acid (GA), an immunomodulator, already known to suppress L. donovani infection, found to up-regulate DUSP4 expression during L. donovani infection. On the other hand, GA failed to increase Th1 cytokine production and decrease Th2 response during DUSP4 knock-down condition suggesting the key role of DUSP4 while providing protection during L. donovani infection.

• Authors: Shabina Parveen, Atish Roy Chowdhury, Junaid Jibran Jawed, Suchandra Bhattacharyya Majumdar, Bhaskar Saha, Subrata Majumdar
• Journal: Microbes and infection (Microbes Infect) Vol. 20 Issue 2 Pg. 111-121 (02 2018) ISSN: 1769-714X [Electronic] France
• PMID: 29133249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Immunologic Factors
• RNA, Small Interfering
• Nitric Oxide
• Glycyrrhizic Acid
• Protein Tyrosine Phosphatases

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Cytokines (genetics)
• Gene Expression Regulation (drug effects)
• Glycyrrhizic Acid (administration & dosage, pharmacology)
• Humans
• Immunologic Factors (administration & dosage, pharmacology)
• Immunomodulation
• Leishmania donovani (physiology)
• Leishmaniasis, Visceral (enzymology, immunology, parasitology)
• Macrophages (immunology, parasitology)
• Mice
• Mice, Inbred BALB C
• Nitric Oxide (analysis)
• Phosphorylation (drug effects)
• Protein Tyrosine Phosphatases (deficiency, genetics, metabolism)
• RNA, Small Interfering (administration & dosage)
• THP-1 Cells
• Th1 Cells (metabolism)
• Th2 Cells (metabolism)