TNF receptor 1, IL-1 receptor, and iNOS genetic knockout mice are not protected from anthrax infection.
Anthrax produces at least two toxins that cause an intense systemic inflammatory response, edema, shock, and eventually death. The relative contributions of various elements of the immune response to mortality and course of disease progression are poorly understood. We hypothesized that knockout mice missing components of the immune system will have an altered response to infection. Parent strain mice and knockouts were challenged with LD95 of anthrax spores (5 x 10(6)) administered subcutaneously. Our results show that all genetic knockouts succumbed to anthrax infection at the same frequency as the parent. TNF antibody delayed death but TNF receptor 1 knockout had no effect. IL-1 receptor or iNOS knockouts died sooner. Anthrax was more abundant in the injection site of TNF-alpha and iNOS knockouts compared to parent suggesting that attenuated cellular response increases rate of disease progression. With the exception of edema and necrosis at the injection site pathological changes in internal organs were not observed.
Kalns
John
J
Davis Hyperbaric Laboratory, 2602 West Gate Road, Brooks Air Force Base, TX 78235-5252, USA. john.kalns@brooks.af.mil
Scruggs
Julie
J
Millenbaugh
Nancy
N
Vivekananda
Jeeva
J
Shealy
David
D
Eggers
Jeffrey
J
Kiel
Johnathan
J
D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse