A Novel Function for the Streptococcus pneumoniae Aminopeptidase N: Inhibition of T Cell Effector Function through Regulation of TCR Signaling
| Autor: | Derek Parsonage, Elizabeth Domzalski, Martha A. Alexander-Miller, Lance K. Blevins, Melissa B. Oliver, W. Edward Swords |
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| Rok vydání: | 2017 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine T cell Immunology Population Aminopeptidase Microbiology 03 medical and health sciences Immune system medicine Immunology and Allergy education Original Research Cytolytic granule education.field_of_study aminopeptidase Effector Chemistry immune regulation 3. Good health 030104 developmental biology medicine.anatomical_structure Tumor necrosis factor alpha lcsh:RC581-607 signaling pneumococcus CD8 |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 8 (2017) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.01610 |
| Popis: | Streptococcus pneumoniae (Spn) causes a variety of disease states including fatal bacterial pneumonia. Our previous finding that introduction of Spn into an animal with ongoing influenza virus infection resulted in a CD8+ T cell population with reduced effector function gave rise to the possibility of direct regulation by pneumococcal components. Here, we show that treatment of effector T cells with lysate derived from Spn resulted in inhibition of IFNγ and tumor necrosis factor α production as well as of cytolytic granule release. Spn aminopeptidase N (PepN) was identified as the inhibitory bacterial component and surprisingly, this property was independent of the peptidase activity found in this family of proteins. Inhibitory activity was associated with reduced activation of ZAP-70, ERK1/2, c-Jun N-terminal kinase, and p38, demonstrating the ability of PepN to negatively regulate TCR signaling at multiple points in the cascade. These results reveal a novel immune regulatory function for a bacterial aminopeptidase. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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