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

Jun Sik Lee,Sung Hak Chun,Jin Wook Park,Tae Kwun Ha,Soo Kyung Jeong,Chang-Min Lee,Yong Kyoo Shin,In Duk Jung,Dae Jin Kim,Yeong-Min Park

doi:10.1186/1471-2180-10-263

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.

Highlights

Typhoid, which is caused by Salmonella enterica serovar Typhimurium, remains a major health concern worldwide
The findings presented suggest that OmpA-sal induces activation of Dendritic cells (DCs) and initiates an adaptive immune response by polarizing T-cell development to a Th1 response, information which will prove crucial in the development of a S. enterica serovar Typhimurium vaccine
OmpA-sal induces DC maturation We purified OmpA-sal from E. coli and assessed its cytotoxicity on DCs because the purified OmpA-sal was derived from S. enterica serovar Typhimurim

Summary

Introduction

Typhoid, which is caused by Salmonella enterica serovar Typhimurium, remains a major health concern worldwide. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play key roles in the regulation of immune responses to a variety of antigens and immune sentinels as initiators of T cell responses against microbial pathogens [1,2,3]. Activated DCs are targeted to secondary lymphoid organs and toward T cell activation by antigen presentation [4,5]. DCs can capture degraded bacteria or protein of bacteria and present their antigens on major histocompatibility complex (MHC) class molecules to T cells [6]. An adaptive immune response that targets bacteria-derived antigens is initiated.

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