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Class I myosin Myo1e regulates TLR4-triggered macrophage spreading, chemokine release, and antigen presentation via MHC class II
- Source :
- European journal of immunology. 45(1)
- Publication Year :
- 2014
-
Abstract
- TLR-mediated recognition of microbial danger induces substantial changes in macrophage migration, adherence and phagocytosis. Recently, we described the LPS-regulated phosphorylation of many cytoskeleton-associated proteins by phosphoproteomics. The functional role of these cytoskeletal and motor proteins in innate immune cell responses is largely unexplored. Here, we first identified both long-tailed class I myosins Myo1e and Myo1f as important contributors to LPS-triggered macrophage spreading. Mouse bone marrow-derived macrophages and dendritic cells (DCs) deficient in Myo1e selectively secreted increased amounts of the chemokine CCL2. In addition, the cell surface expression of MHC class II (MHC-II) on both cell types was reduced in the absence of Myo1e. However, transcriptional changes in CCL2 and MHC-II were not observed in the absence of Myo1e, indicating that Myo1e regulates specific intracellular transport processes. The capacity of macrophages and DCs lacking Myo1e to stimulate antigen-specific CD4+ T-cell proliferation was impaired, consistent with the reduced MHC-II surface protein levels. Surprisingly, in Myo1e-deficient DCs, the proteolytic cleavage of endocytosed antigen was also increased. Together, our results provide evidence for a non-redundant function of the motor protein Myo1e in the regulation of TLR4-controlled, cytoskeleton-associated functional properties of macrophages and DCs, and in induction of a full MHC-II-restricted adaptive immune response.
- Subjects :
- CD4-Positive T-Lymphocytes
Lipopolysaccharides
Mice, Knockout
Antigen Presentation
Macrophages
Primary Cell Culture
Histocompatibility Antigens Class II
chemical and pharmacologic phenomena
Bone Marrow Cells
Dendritic Cells
Myosins
Article
Mice, Inbred C57BL
Toll-Like Receptor 4
Mice
Myosin Type I
Gene Expression Regulation
Animals
Chemokine CCL2
Cytoskeleton
Cell Proliferation
Signal Transduction
Subjects
Details
- ISSN :
- 15214141
- Volume :
- 45
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- European journal of immunology
- Accession number :
- edsair.pmid..........e597616783f3a8736041a92ef317be90