Abstract
The c-Jun N-terminal kinase-mitogen-activated protein kinase (JNK-MAPK) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. To understand the role of the JNK-MAPK pathway during bacterial infection, an in vivo model organism Caenorhabditis elegans was used. In order to check the involvement of the JNK-MAPK pathway, the survival rate of C. elegans wild type (WT), and JNK-MAPK pathway mutant worms’ upon exposure to selective Gram-positive and Gram-negative pathogenic bacteria, was studied. Among the pathogens, Shigella flexneri M9OT was found to efficiently colonize inside the WT and JNK-MAPK pathway mutant worms. qPCR studies had suggested that the above pathway-specific genes kgb-2 and jnk-1 were prominently responsible for the immune response elicited by the host during the M9OT infection. In addition, daf-16, which is a major transcription factor of the insulin/insulin growth factor-1 signaling (IIS) pathway, was also found to be involved during the host response. Crosstalk between IIS and JNK-MAPK pathways has probably been involved in the activation of the host immune system, which consequently leads to lifespan extension. Furthermore, it is also observed that daf-16 activation by JNK-MAPK pathway leads to antimicrobial response, by activating lys-7 expression. These findings suggest that JNK-MAPK is not the sole pathway that enhances the immunity of the host. Nonetheless, the IIS pathway bridges the JNK-MAPK pathway that influences in protecting the host in counter to the M9OT infection.
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Abbreviations
- JNK:
-
C-Jun N-terminal kinase
- MAPK:
-
Mitogen-activated protein kinase
- IIS:
-
Insulin/insulin growth factor-1 signaling
- KGB-1:
-
Kinase, germline helicase binding
- MEK-1:
-
Mitogen-activated protein kinase kinase
- JKK-1:
-
C-Jun N-terminal kinase kinase
- DAF-16:
-
Abnormal dauer formation
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Acknowledgements
We thank Caenorhabditis Genetics Center, which is funded by the National Institute of Health, and the National Center for Research Resources for providing C. elegans strains and E. coli OP50. SMP thanks the Department of Science and Technology (No. SR/FT/LS-83/2009(G)) for financial assistance through project JRF. SMP also would like to thank Udayakumar Prithika and Sekar Balaji for their constant support during the course of the experiment. The authors also thankfully acknowledge the computational facility provided by the Alagappa University Bioinformatics Infrastructure Facility (funded by DBT, Government of India; Grant No. BT/BI/25/001/2006). The Instrumentation Facility provided by the Department of Science and Technology, Government of India, through PURSE [Grant No.SR/S9Z-23/2010/42 (G)] and FIST (Grant No. SR-FST/LSI-087/2008) and University Grants Commission, New Delhi, through SAP-DRS1 [Grant No. F.3-28/2011 (SAP-II)] is greatly acknowledged. The authors also thank Dr. Maria Rescigno, European Institute of Oncology, Milano, Italy, for providing S. flexneri 5a M9OT:: DsRed strain.
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The study received partial financial support through the Extramural Research grants from DBT (BT/PR14932/MED/29/233/2010), ICMR (Sanction No: 5/3/3/13/2010-ECD-I), DST-SERB (No. SR/SO/AS-80/2010), UGC Major Research Project (No. 42-222/2013 (SR)), and CSIR (No. 37(1460)/11/EMR-II), New Delhi, India, by KB.
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Marudhupandiyan, S., Balamurugan, K. Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans . Immunol Res 65, 609–621 (2017). https://doi.org/10.1007/s12026-016-8879-6
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DOI: https://doi.org/10.1007/s12026-016-8879-6