Polyamine Transport Protein PotD Protects Mice against Haemophilus parasuis and Elevates the Secretion of Pro-Inflammatory Cytokines of Macrophage via JNK–MAPK and NF–κB Signal Pathways through TLR4
Open Access
- 14 December 2019
- Vol. 7 (4), 216
- https://doi.org/10.3390/vaccines7040216
Abstract
The potD gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system potABCD, encodes the bacterial substrate-binding subunit of the polyamine transport system. In this study, we found PotD in Haemophilus (Glaesserella) parasuis could actively stimulate both humoral immune and cellular immune responses and elevate lymphocyte proliferation, thus eliciting a Th1-type immune response in a murine immunity and infection model. Stimulation of Raw 264.7 macrophages with PotD validated that Toll-like receptor 4, rather than 2, participated in the positive transcription and expression of pro-inflammatory cytokines IL–1β, IL–6, and TNF–α using qPCR and ELISA. Blocking signal-regulated JNK–MAPK and RelA(p65) pathways significantly decreased PotD-induced pro-inflammatory cytokine production. Overall, we conclude that vaccination of PotD could induce both humoral and cellular immune responses and provide immunoprotection against H. parasuis challenge. The data also suggest that Glaesserella PotD is a novel pro-inflammatory mediator and induces TLR4-dependent pro-inflammatory activity in Raw 264.7 macrophages through JNK–MAPK and RelA(p65) pathways.Funding Information
- National Key Research and Development Program of China (2016YFD0500800)
This publication has 57 references indexed in Scilit:
- Pattern Recognition Receptors and Control of Innate Immunity: Role of Nucleic AcidsCurrent Pharmaceutical Biotechnology, 2019
- Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetrationNature Communications, 2011
- The role of pattern-recognition receptors in innate immunity: update on Toll-like receptorsNature Immunology, 2010
- Mucosal Immunization with Polyamine Transport Protein D (PotD) Protects Mice Against Nasopharyngeal Colonization with Streptococcus pneumoniaeExperimental Biology and Medicine, 2009
- Immunization with Polyamine Transport Protein PotD Protects Mice against Systemic Infection with Streptococcus pneumoniaeInfection and Immunity, 2006
- Cellular location of polyamine transport protein PotD inStreptococcus pneumoniaeFEMS Microbiology Letters, 2006
- Involvement of potD in Streptococcus pneumoniae Polyamine Transport and PathogenesisInfection and Immunity, 2006
- Polyamine metabolism revisitedEuropean Journal of Gastroenterology & Hepatology, 2001
- Spermidine-preferential Uptake System in Escherichia coliOnline Journal of Public Health Informatics, 1996
- Crystallization and preliminary X-ray analysis of the primary receptor (PotD) of the polyamine transport system in Escherichia coliActa crystallographica. Section D, Structural biology, 1996