Accession Number : ADA433068


Title :   Human Leukocyte Antigen-DQ8 Transgenic Mice: A Model to Examine the Toxicity of Aerosolized Staphylococcal Enterotoxin B


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD VIROLOGY DIV


Personal Author(s) : Roy, Chad J ; Warfield, Kelly L ; Welcher, Brent C ; Gonzales, Raoul F ; Larsen, Tom ; Hanson, Julie ; David, Chella S ; Krakauer, Theresa ; Bavari, Sina


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a433068.pdf


Report Date : 30 Nov 2004


Pagination or Media Count : 11


Abstract : Staphylococcal enterotoxins (SEs) belong to a large group of bacterial exotoxins that cause severe immunopathologies, especially when delivered as an aerosol. SEs elicit the release of lethal amounts of cytokines by binding to major histocompatibility complex (MHC) class II and cross-linking susceptible T-cell receptors. Efforts to develop effective therapeutic strategies to protect against SEs delivered as an aerosol have been hampered by the lack of small animal models that consistently emulate human responses to these toxins. Here, we report that human leukocyte antigen-DQ8 (HLA-DQ8) transgenic (Tg) mice, but not littermate controls, succumbed to lethal shock induced by SEB aerosols without potentiation. Substantial amounts of perivascular edema and inflammatory infiltrates were noted in the lungs of Tg mice, similar to the pathology observed in nonhuman primates exposed by aerosol to SEB. Furthermore, the observed pathologies and lethal shock correlated with an upsurge in proinflammatory cytokine mRNA gene expression in the lungs and spleens, as well as with marked increases in the levels of proinflammatory circulating cytokines in the Tg mice. Unlike the case for littermate controls, telemetric evaluation showed significant hypothermia in Tg mice exposed to lethal doses of SEB. Taken together, these results show that this murine model will allow for the examination of therapeutics and vaccines developed specifically against SEB aerosol exposure and possibly other bacterial superantigens in the context of human MHC class II receptors.


Descriptors :   *TOXICITY , *ENTEROTOXINS , *LETHALITY , *ANTIGENS , *RECEPTOR SITES(PHYSIOLOGY) , *STAPHYLOCOCCUS , *EXOTOXINS , TEST AND EVALUATION , REPRINTS , AEROSOLS , HUMANS , BACTERIA , CROSSLINKING(CHEMISTRY) , SHOCK , LUNG , THERAPY , GENES , ANIMALS , PATHOLOGY , PRIMATES , RESPONSE(BIOLOGY) , MICE , T LYMPHOCYTES , BIOLOGICAL AEROSOLS , CIRCULATION , HYPOTHERMIA , LETHAL DOSAGE , TOXINS AND ANTITOXINS , VACCINES , SPLEEN , TELEMETER SYSTEMS , HISTOCOMPATIBILITY , CYTOKINES


Subject Categories : Medicine and Medical Research
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE