Macrophage infection with combinations of BCG mutants reduces induction of TNF-α, IL-6, IL-1β and increases IL-4

Tuberculosis (TB) is the most prevalent infectious disease worldwide, with no fully effective vaccine yet available. Considering that BCG strains devoid of the BCG1416c or BCG1419c genes afforded protection in mice versus highly virulent M. tuberculosis challenge, or in chronic infection models comp...

Full description

Saved in:

Bibliographic Details
Published in:	Tuberculosis (Edinburgh, Scotland) Scotland), 2019-03, Vol.115, p.42-48
Main Authors:	Segura-Cerda, Cristian Alfredo, Aceves-Sánchez, Michel de Jesús, Pérez-Koldenkova, Vadim, Flores-Valdez, Mario Alberto
Format:	Article
Language:	eng
Subjects:	Animals Bacillus Calmette-Guerin vaccine BCG BCG Vaccine Chronic infection Combined vaccines Cytokines Design of experiments Experimental design Host-Pathogen Interactions IL-1β IL-4 IL-6 Infections Infectious diseases Inflammation Interleukin 4 Interleukin 6 Interleukin-1beta - metabolism Interleukin-4 - metabolism Interleukin-6 - metabolism Interleukins - metabolism Macrophages Macrophages - microbiology Mice Mixed-infection Mutants Mutation - physiology Mycobacterium bovis - genetics Mycobacterium bovis - physiology Mycobacterium tuberculosis Mycobacterium tuberculosis - genetics Synergistic effect TNF-α Tuberculosis Tuberculosis - metabolism Tuberculosis - prevention & control Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Vaccines
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Tuberculosis (TB) is the most prevalent infectious disease worldwide, with no fully effective vaccine yet available. Considering that BCG strains devoid of the BCG1416c or BCG1419c genes afforded protection in mice versus highly virulent M. tuberculosis challenge, or in chronic infection models compared to BCG, respectively, we hypothesized that a synergistic effect of these strains might occur and provide enhanced protection against TB. Herein, we evaluated this hypothesis throughout an experimental design approach, where different combinations of these strains were tested for their capacity to induce cytokines in vitro, compared to individual strains. Our results show that mixed-infection of murine macrophages using these strains significantly decreases induction of TNF-α, IL-1β, IL-6 but increases IL-4 induction compared with individual strains. These results suggest the existence of interaction effects during infection, which reduce induction of pro-inflammatory cytokines, even though individual intracellular replication is not altered when strains are combined. This is the first report of the evaluation of a potential whole-live combined vaccine against tuberculosis, which paradoxically seems to reduce production of pro-inflammatory cytokines while induces IL-4, leading us to further hypothesize that this combination might contribute as a therapeutic vaccine to reduce inflammation in severe TB cases.
ISSN:	1472-9792 1873-281X