Inhibition of airway eosinophilia and pulmonary pathology in a mouse model of allergic asthma by the live vaccine strain of Francisella tularensis.
BACKGROUND
It has been suggested that exposure to certain microbes and their products, particularly during neonatal and early childhood periods, may shift the immune response towards a T-helper cell (Th) 1 phenotype and thereby prevent the development of and/or alleviate the clinical symptoms of allergic airway diseases.


OBJECTIVE
We evaluated the ability of the live vaccine strain (LVS) of Francisella tularensis to suppress airway eosinophilia and pulmonary pathology in a murine model of allergic airway disease.


METHODS
C57BL/6 mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 1 and 14, and challenged intranasally (i.n.) with OVA on day 21 or thereafter. Some sensitized mice were i.n. treated with live LVS or its cell-free sonicate extract (CFSE) before i.n. OVA challenge. Bronchoalveolar lavage fluid, regional lymph node cells, lung tissues and serum samples were collected 3-7 days after the i.n. challenge.


RESULTS
Intranasal and, to a lesser degree, intradermal immunization of OVA-sensitized mice with LVS suppressed the development of airway eosinophilia and associated pulmonary pathology induced by i.n. OVA challenge. Moreover, CFSE prepared from LVS showed a similar inhibitory effect whereas neither LPS nor DNA purified from F. tularensis LVS had such an effect. The inhibition was associated with the reduction in mRNA expression and protein levels of Th2 cytokines IL-5 and IL-13 in the lungs and the enhanced production of OVA-induced IFN-gamma by local draining lymph node cells, but not with the serum levels of OVA-specific IgG1 or IgE.


CONCLUSIONS
F. tularensis LVS is capable of suppressing allergic airway inflammation probably through a Th1-mediated suppression of an ongoing Th2 response mechanism, and raises the possibility of exploring LVS and its components as potential therapeutic modalities for human allergic asthma.
KuoLee
R
R
Institute for Biological Sciences, National Research Council Canada, Ottawa, ON, Canada.
Zhou
H
H
Harris
G
G
Zhao
X
X
Qiu
H
H
Patel
G B
GB
Chen
W
W
D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005604:Francisella tularensis / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
D001428:Bacterial Vaccines; D016207:Cytokines; D004269:DNA, Bacterial; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin