Evaluation of Th1/Th2-Related Immune Response against Recombinant Proteins of Brucella abortus Infection in Mice

J Microbiol Biotechnol. 2016 Jun 28;26(6):1132-9. doi: 10.4014/jmb.1512.12046.

Abstract

Brucellosis is a zoonotic disease caused by Brucella, a genus of gram-negative bacteria. Cytokines have key roles in the activation of innate and acquired immunities. Despite several research attempts to reveal the immune responses, the mechanism of Brucella infection remains unclear. Therefore, immune responses were analyzed in mice immunized with nine recombinant proteins. Cytokine production profiles were analyzed in the RAW 264.7 cells and naive splenocytes after stimulation with three recombinant proteins, metal-dependent hydrolase (r0628), bacterioferritin (rBfr), and thiamine transporter substrate-binding protein (rTbpA). Immune responses were analyzed by ELISA and ELISpot assay after immunization with proteins in mice. The production levels of NO, TNF-α, and IL-6 were time-dependently increased after having been stimulated with proteins in the RAW 264.7 cells. In naive splenocytes, the production of IFN-γ and IL-2 was increased after stimulation with the proteins. It was concluded that two recombinant proteins, r0628 and rTbpA, showed strong immunogenicity that was induced with Th1-related cytokines IFN-γ, IL-2, and TNF-α more than Th2-related cytokines IL-6, IL-4, and IL-5 in vitro. Conversely, a humoral immune response was activated by increasing the number of antigen-secreting cells specifically. Furthermore, these could be candidate diagnosis antigens for better understanding of brucellosis.

Keywords: Brucella abortus; cytokine; immunogenicity; recombinant protein.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Bacterial Proteins / immunology
  • Brucella abortus / chemistry
  • Brucella abortus / immunology*
  • Brucellosis / immunology*
  • Brucellosis / microbiology
  • Carrier Proteins / immunology
  • Cytochrome b Group / immunology
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Ferritins / immunology
  • Hydrolases / immunology
  • Immunity, Humoral
  • Immunization
  • Immunoglobulin G
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • RAW 264.7 Cells
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Spleen / cytology
  • Spleen / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Cytochrome b Group
  • Cytokines
  • Immunoglobulin G
  • Interleukin-2
  • Interleukin-6
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • thiamine-binding protein
  • Interferon-gamma
  • Ferritins
  • bacterioferritin
  • Hydrolases