Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-5-3
pubmed:abstractText
Previous studies have shown that IFN-gamma, TNF-alpha and NOS-2, but not B cells, are crucial for host defense against primary systemic infection with the attenuated live vaccine strain (LVS) of Francisella tularensis. In this study, we examined the importance of these and additional immune components in host resistance against infection with virulent strains of F. tularensis initiated by systemic and airborne routes. Wild-type (WT) mice and mice deficient in IFN-gamma, TNFR1R2, NOS-2, or B cells were equally susceptible to low dose ( approximately 10 colony forming units) aerosol or intradermal challenge with virulent type B F. tularensis, and succumbed to the infection between days 6 and 8 post-inoculation. Quantitative bacteriology showed that IFN-gamma-/- and B cell-/- mice consistently harbored up to one log(10) more bacteria in their lungs, spleens and livers than WT mice at day 5 post aerosol exposure. Surprisingly, however, compared to other strains of KO mice and WT control mice, IFN-gamma-/- mice showed only mild liver damage as assessed by histopathology and liver function tests. Additional experiments established that even mice with broad immunodeficiency (SCID, neutropenic, splenectomized or thymectomized mice and mice treated with corticosteroid) were no more susceptible to aerosol-initiated infection with virulent type B or type A F. tularensis than immunosufficient control mice. Combined, our results indicate that, unlike LVS, normal type A and type B F. tularensis strains are so extremely virulent that even immunocompetent mice are virtually defenseless to low dose aerosol and intradermal challenges with them.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0882-4010
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-8
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed-meshheading:15120157-Aerosols, pubmed-meshheading:15120157-Alanine Transaminase, pubmed-meshheading:15120157-Albumins, pubmed-meshheading:15120157-Animals, pubmed-meshheading:15120157-Aspartate Aminotransferases, pubmed-meshheading:15120157-B-Lymphocytes, pubmed-meshheading:15120157-Colony Count, Microbial, pubmed-meshheading:15120157-Disease Susceptibility, pubmed-meshheading:15120157-Francisella tularensis, pubmed-meshheading:15120157-Injections, Intradermal, pubmed-meshheading:15120157-Interferon-gamma, pubmed-meshheading:15120157-Liver, pubmed-meshheading:15120157-Lung, pubmed-meshheading:15120157-Mice, pubmed-meshheading:15120157-Mice, Knockout, pubmed-meshheading:15120157-Mice, SCID, pubmed-meshheading:15120157-Nitric Oxide Synthase, pubmed-meshheading:15120157-Nitric Oxide Synthase Type II, pubmed-meshheading:15120157-Receptors, Tumor Necrosis Factor, pubmed-meshheading:15120157-Spleen, pubmed-meshheading:15120157-Survival Analysis, pubmed-meshheading:15120157-Tularemia, pubmed-meshheading:15120157-Urea, pubmed-meshheading:15120157-Virulence
pubmed:year
2004
pubmed:articleTitle
Susceptibility of immunodeficient mice to aerosol and systemic infection with virulent strains of Francisella tularensis.
pubmed:affiliation
Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario, Canada K1A 0R6. wangxue.chen@nrc.gc.ca
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't