Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: a new mouse model.
Murine models for bacterial superantigens like staphylococcal enterotoxin B (SEB) have to date been rather cumbersome. The reasons include: (1) necessary use of potentiating agents such as actinomycin D, d-galactosamine, lipopolysaccharide (LPS), or viruses; (2) high toxin amounts required to elicit effects; and/or (3) generation of phenotypic-stable transgenic animals. Our study employed readily available C3H/HeJ (TLR4 negative, LPS-nonresponsive) mice with intranasal and intraperitoneal administration of low microgram quantities of SEB. These animals responded to SEB with severe lung inflammation and hypothermia, culminating in death. A survey of cytokines/chemokines in sera and lungs after lethal intoxication revealed that monocyte chemoattractant protein-1 and interleukin-2 were associated with effects in this model. In contrast, SEB had minimal effects upon congenic (TLR4 positive, LPS-responsive) C3H/OuJ mice. Lethality of SEB in C3H/HeJ mice was neutralized with SEB-specific antibodies, suggesting potential utility of this model for future therapeutic studies.
Huzella
Louis M
LM
Pathology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, United States.
Buckley
Marilyn J
MJ
Alves
Derron A
DA
Stiles
Bradley G
BG
Krakauer
Teresa
T
D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D006651:Histocytochemistry / Q000662:veterinary; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D010865:Pilot Projects; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*
D000942:Antigens, Bacterial; D018932:Chemokine CCL2; D004768:Enterotoxins; D007376:Interleukin-2; C031818:enterotoxin B, staphylococcal