The influence of interferon-β supplemented human dendritic cells on BCG immunogenicity

Sally A F El-Sahrigy; Azza M O Abdel Rahman; Dalia Y Samaha; Nesrine A Mohamed; Sally M Saber; Hala A Talkhan; Ghada A Ismail; Essam M Ibraheem; Emad M Riad

doi:10.1016/j.jim.2018.03.003

The influence of interferon-β supplemented human dendritic cells on BCG immunogenicity

J Immunol Methods. 2018 Jun:457:15-21. doi: 10.1016/j.jim.2018.03.003. Epub 2018 Mar 6.

Authors

Sally A F El-Sahrigy¹, Azza M O Abdel Rahman¹, Dalia Y Samaha², Nesrine A Mohamed³, Sally M Saber⁴, Hala A Talkhan², Ghada A Ismail⁴, Essam M Ibraheem⁵, Emad M Riad⁵

Affiliations

¹ Pediatrics Department, Medical Research Division, National Research Centre, Cairo, Egypt.
² Clinical Pathology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
³ Clinical Pathology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: alynesrine@yahoo.com.
⁴ Clinical Pathology & Microbiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁵ Animal Health Research Institute (AHRI), Dokki, Egypt.

PMID: 29522775
DOI: 10.1016/j.jim.2018.03.003

Abstract

Introduction: Tuberculosis (TB) remains a huge worldwide burden, despite extensive vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is inadequate to protect the human population against TB. This underscore the critical necessitate to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection.

Aim of the work: To examine whether the exogenous addition of IFN-β could improve dendritic cell (DC) response to Mycobacterium bovis (M. bovis) and to evaluate the effect induced by the infection of human DCs with M. bovis (with and without IFN-β) and Mycobacterium tuberculosis (Mtb) on DC viability as well as to compare the ability of BCG and Mtb to provide DCs with a Th1-polarizing capacity through the assessment of the immunoregulatory cytokines interleukin (IL)-12, IL-10 and interferon-gamma (IFN-γ).

Methods: Immature DCs (iDCs) were generated in vitro using peripheral blood monocytes separated by anti-CD14-conjugated microbeads in the presence of granulocyte-macrophage-colony-stimulating factor (GM-CSF) and IL-4, cultured cells were analyzed using flow cytometry, then we tested DC viability after inoculation with M. bovis (with and without IFN-β pretreatment) and Mtb using light microscopic examination and trypan blue exclusion method. Additionally, supernatants from infected-DCs cultures were analyzed for IFN-γ, IL-12 and IL-10 by ELISA.

Results: The viability of BCG-infected DCs was significantly higher than that of Mtb-infected DCs (61.55% vs 52.10%). BCG-infected DC produced significantly more IL-12 (p = 0.02) and less IL-10 (p = 0.01) compared with Mtb-infected cells. IFN-β-pretreated BCG-infected DCs produced significantly larger amounts of IL-12 than did BCG-infected DCs (p = 0.03) and Mtb-infected cells (p < 0.001).

Conclusion: IFN-β improves DC functions following BCG infection, thus assuming that IFN-β could be used as a vaccine adjuvant.

Keywords: Bacillus Calmette-Guérin; Cytokines; Dendritic cells; Interferon-beta; Tuberculosis.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Adult
BCG Vaccine / immunology*
Cell Survival
Cells, Cultured
Dendritic Cells / drug effects*
Dendritic Cells / immunology*
Dendritic Cells / microbiology
Humans
Immunogenicity, Vaccine
Interferon-beta / pharmacology*
Interferon-gamma / metabolism
Interleukin-10 / metabolism
Interleukin-12 / metabolism
Lymphocyte Activation
Middle Aged
Mycobacterium bovis
Young Adult

Substances

Adjuvants, Immunologic
BCG Vaccine
IFNG protein, human
IL10 protein, human
Interleukin-10
Interleukin-12
Interferon-beta
Interferon-gamma