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


RESULTS
We 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.


CONCLUSIONS
Our 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.
Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, Pusan National University School of Medicine, Yang-san 626-770, South Korea.
Jun Sik
JS
Lee
In Duk
ID
Jung
Chang-Min
CM
Lee
Jin Wook
JW
Park
Sung Hak
SH
Chun
Soo Kyung
SK
Jeong
Tae Kwun
TK
Ha
Yong Kyoo
YK
Shin
Dae Jin
DJ
Kim
Yeong-Min
YM
Park
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D001425:Bacterial Outer Membrane Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C078167:OMPA outer membrane proteins