Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization

Abstract

BackgroundTyphoid, which is caused by Salmonella enterica serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of Salmonella have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis.ResultsWe purified OmpA from S. enterica serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system.ConclusionsOur findings suggest that OmpA-sal modulates the adaptive immune responses to S. enterica serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective S. enterica serovar Typhimurium vaccines and immunotherapy adjuvant.

RecombinantSalmonella typhimuriumouter membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy

“…However, immunogenicity to OmpA has been studied in murine or human macrophages and dendritic cells (DCs). OmpA of Klebsiella pneumoniae binds and activates human macrophages to produce IL‐1β, IL‐8, IL‐10, IL‐12 and tumour necrosis factor (TNF)‐α and nitric oxide by murine macrophage cell lines , as well as eliciting cytotoxic T lymphocyte (CTL) responses to human DCs , while OmpA of S. typhimurium activates mouse DC cells and helps in Th1 polarization . In line with these observations, a higher SF CTL response in patients with ReA/uSpA to rOmpA‐sal was observed.…”

Eight Stranded β -Barrel and Related Outer Membrane Proteins: Role in Bacterial Pathogenesis

“…This immunogenicity has application in the use of OmpA as a vaccine candidate in the protection against pathogens where OmpA plays a role in attachment and virulence. S. typhimurium OmpA induced functional and phenotypic maturation of dendritic cells and the activation of ERK1/2 and p38 MAPK via TLR4; activating T cells via a Th1 response [50]. In addition to the potential use of OmpA protein as an immunoprophylactic agent [34], the ompA gene was one of two components of a DNA vaccine that protected against Klebsiella pneumoniae in mice [51].…”

Cloning, expression and purification of the outer membrane protein28 of Salmonella enterica serovar Typhimurium for subunit vaccine development - a short communication

“…Vaccination is an important strategy to eliminate the condition, but the available vaccines suffer from limitations, such as short-term immunity and virulence restoration. The outer membrane proteins (Omps) from Salmonella have been proven to have good immunogenicity (LEE et al, 2010;GIL-CRUZ et al, 2009). Since that discovery, Salmonella Omps have been characterized (HAMID and JAIN, 2008) and targeted for protection (JHA et al, 2015;SAXENA et al, 2012;BHAT and JAIN, 2010).…”