| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Nakhasi, Hira L. Allman, Windy R. Liu, Lunhua Siddiqui, Shafiuddin Coleman, Adam S. Takeda, Kazuyo Akkoyunlu, Mustafa Uslu, Kadriye Bhattacharya, Parna Yano, Masahide Dey, Ranadhir |
| Description |
Author Affiliation: Allman WR ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); Dey R ( Division of Emerging and Transfusion Transmitted Diseases, US Food and Drug Administration, Silver Spring, MD 20993); Liu L ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); Siddiqui S ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); Coleman AS ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); Bhattacharya P ( Division of Emerging and Transfusion Transmitted Diseases, US Food and Drug Administration, Silver Spring, MD 20993); Yano M ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); Uslu K ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); Takeda K ( Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993.); Nakhasi HL ( Division of Emerging and Transfusion Transmitted Diseases, US Food and Drug Administration, Silver Spring, MD 20993); Akkoyunlu M ( Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, US Food and Drug Administration, Silver Spring, MD 20993); |
| Abstract |
The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO ΜÏ s expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-ß and responded poorly to TLR agonists. Analysis of ΜÏ phenotype revealed that, in the absence of TACI, ΜÏ s adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4R , CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO ΜÏ than in WT cells. Confirming their M2 phenotype, TACI-KO MÏ s were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT ΜÏ s to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence MÏ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient ΜÏ s. Moreover, treatment of ΜÏ s with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
30 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-07-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Leishmania Pathogenicity Leishmaniasis Immunology Macrophages Transmembrane Activator And CAML Interactor Protein Metabolism Animals Antigens, CD14 B-Cell Activating Factor Cell Proliferation Gene Expression Regulation Ligands Mice Mice, Inbred C57BL Mice, Knockout Phenotype Phosphorylation Signal Transduction Genetics Tumor Necrosis Factor Ligand Superfamily Member 13 Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
