A subunit vaccine based on rH-NS induces protection against Mycobacterium tuberculosis infection by inducing the Th1 immune response and activating macrophages
| Autor: | Hong Cai, Bowen Pan, Zhu Guan, Yuan Liu, Linfei Duan, Zhenjun Yang, Su-Ting Chen |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Interleukin 2 biology Chemistry medicine.medical_treatment 030106 microbiology Biophysics Spleen General Medicine biology.organism_classification Biochemistry Microbiology Mycobacterium tuberculosis 03 medical and health sciences TLR2 030104 developmental biology medicine.anatomical_structure Cytokine Immunology TLR4 medicine Macrophage Adjuvant medicine.drug |
| Zdroj: | Acta Biochimica et Biophysica Sinica. 48:909-922 |
| ISSN: | 1672-9145 |
| DOI: | 10.1093/abbs/gmw078 |
| Popis: | Mycobacterium tuberculosis (Mtb) is a Gram-positive pathogen which causes tuberculosis in both animals and humans. All tested rH-NS formulations induced a specific Th1 response, as indicated by increased production of interferon γ (IFN-γ) and interleukin 2 (IL-2) by lymphocytes in the spleen of mice which were immunized with rH-NS alone or with rH-NS and the adjuvant cyclic GMP-AMP (cGAMP). Serum from mice immunized with rH-NS with or without adjuvant also had higher levels of IL-12p40 and TNF-α, compared with those from control mice immunized with phosphate-buffered saline. Both vaccines increased protective efficacy in mice which were challenged with Mtb H37Rv, as measured by reduced relative CFU counts in the lungs. We found that rH-NS induced the production of TNF-α, IL-6, and IL-12p40, which relied on the activation of mitogen-activated protein kinases by stimulating the rapid phosphorylation of ERK1/2, p38, and JNK, and on the activation of transcription factor NF-κB in macrophages. Additionally, we also found that rH-NS could interact with TLR2 but not TLR4 in pull-down assays. The rH-NS-induced cytokine production from TLR2-silenced RAW264.7 cells was lower than that from BALB/c macrophages. Prolonged exposure (>24 h) of RAW264.7 cells to rH-NS resulted in a significant enhancement in IFN-γ-induced MHC II expression, which was not found in shTLR2-treated RAW264.7 cells. These results suggest that rH-NS is a TLR2 agonist which induces the production of cytokines by macrophages and up-regulates macrophage function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|