NDLI: Differential activation of inflammatory pathways in testicular macrophages provides a rationale for their subdued inflammatory capacity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lu, Yongning Vijayan, Vijith Tchatalbachev, Svetlin Fijak, Monika Chakraborty, Trinad Bhushan, Sudhanshu Meinhardt, Andreas Fröhlich, Suada
Description	Author Affiliation: Bhushan S ( Department of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany); Tchatalbachev S ( Department of Medical Microbiology, Justus Liebig University Giessen, 35392 Giessen, Germany.); Lu Y ( Department of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany); Fröhlich S ( Department of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany); Fijak M ( Department of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany); Vijayan V ( Department of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany); Chakraborty T ( Department of Medical Microbiology, Justus Liebig University Giessen, 35392 Giessen, Germany.); Meinhardt A ( Department of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany)
Abstract	Spermatogenic cells express cell-specific molecules with the potential to be seen as 'foreign' by the immune system. Owing to the time difference between their appearance in puberty and the editing of the lymphocyte repertoire around birth, local adaptations of the immune system coined immune privilege are required to confer protection from autoattack. Testicular macrophages (TM) play an important role in maintaining testicular immune privilege and display reduced proinflammatory capacity compared with other macrophages. However, the molecular mechanism underlying this macrophage phenotype remained elusive. We demonstrate that TM have a lower constitutive expression of TLR pathway-specific genes compared with peritoneal macrophages. Moreover, in TM stimulated with LPS, the NF-κB signaling pathway is blocked due to lack of IκB ubiquitination and, hence, degradation. Instead, challenge of TM with LPS or polyinosinic-polycytidylic acid induces MAPK, AP-1, and CREB signaling pathways, which leads to production of proinflammatory cytokines such as TNF- , although at much lower levels than in peritoneal macrophages. Pretreatment of TM with inhibitors for MAPKs p38 and ERK1/2 suppresses activation of AP-1 and CREB signaling pathways and attenuates LPS-induced TNF- and IL-10 secretion. High levels of IL-10 production and activation of STAT3 by LPS stimulation in TM indicate a regulatory macrophage phenotype. Our results suggest that TM maintain testicular immune privilege by inhibiting NF-κB signaling through impairment of IκB ubiquitination and a general reduction of TLR cascade gene expression. However, TM do maintain some capacity for innate immune responses through AP-1 and CREB signaling pathways.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	I-kappa B Proteins Metabolism Inflammation Immunology Macrophages Nf-kappa B Antagonists & Inhibitors Testis Animals Cells, Cultured Cyclic Amp Response Element-binding Protein Biosynthesis Extracellular Signal-regulated Map Kinases Immune Tolerance Immunity, Innate Interleukin-10 Secretion Lipopolysaccharides Map Kinase Signaling System Poly I-c Rats, Wistar Stat3 Transcription Factor Cytology Toll-like Receptors Transcription Factor Ap-1 Tumor Necrosis Factor-alpha Ubiquitination P38 Mitogen-activated Protein Kinases Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in