Local pulmonary immunotherapy with siRNA targeting TGFβ1 enhances antimicrobial capacity in Mycobacterium tuberculosis infected mice

Summary In this study we demonstrate that it is possible to shift the immune system during a chronic infection with Mycobacterium tuberculosis . TGFβ and IL10 cytokines inhibit the Th1 response during chronic pulmonary infection with M. tuberculosis . We show that intrapulmonary delivery of siRNA ta...

Full description

Saved in:
Bibliographic Details
Published in:Tuberculosis (Edinburgh, Scotland) Scotland), 2011-01, Vol.91 (1), p.98-106
Main Authors: Rosas-Taraco, Adrian G, Higgins, David M, Sánchez-Campillo, Joaquín, Lee, Eric J, Orme, Ian M, González-Juarrero, Mercedes
Format: Article
Language:English
Subjects:
Animals
Cytokines - immunology
IL-10
Infectious Disease
Interleukin-10 - immunology
Lung - immunology
Lymphocyte Activation
Mice
Mice, Knockout
Mycobacterium tuberculosis - immunology
Pulmonary
Pulmonary/Respiratory
RNA, Small Interfering - pharmacology
siRNA
TGF
Th1 Cells - immunology
Therapy
Transforming Growth Factor beta1 - drug effects
Transforming Growth Factor beta1 - immunology
Tuberculosis
Tuberculosis, Pulmonary - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary In this study we demonstrate that it is possible to shift the immune system during a chronic infection with Mycobacterium tuberculosis . TGFβ and IL10 cytokines inhibit the Th1 response during chronic pulmonary infection with M. tuberculosis . We show that intrapulmonary delivery of siRNA targeting TGFβ1 is able to reduce the pulmonary bacillary load in mice chronically infected with M. tuberculosis : an effect that appears to be partly dependent on IL10 expression. To demonstrate this, we induced gene silencing of tgfβ1 in the lungs of wild type and IL10 knockout mice using a non-invasive aerosolized intrapulmonary delivery of siRNA targeting TGFβ1. Five days after the last treatment with siRNA, the levels of tgfb1 transcripts and TGFβ1 protein were reduced when compared with control groups treated with RNase-free water or non-targeting siRNA. Mice treated with siRNA also had increased expression of the antimicrobial mediators (NO and iNOS) which effectively reduced the bacterial load by 0.17 and 0.47 log10 in C57BL/6 and IL-10 KO mice respectively when compared with their respective control mice. More importantly, the bacterial load in siRNA treated IL-10 KO mice four weeks after the last treatment remained 0.32 log10 lower than in control mice.
ISSN:1472-9792
1873-281X
DOI:10.1016/j.tube.2010.11.004