Interferon protects mice against inhalation anthrax

Abstract

Interferons (IFNs) play a role in innate immunity during many viral, bacterial, and protozoal infections. With the increasing threat of bioterrorist attacks with Bacillus anthracis, its high lethality, and the limited effectiveness of antibiotics, alternative treatments are being studied. Antibodies to protective antigen (PA) are promising, as is IFN. During many bacterial infections, production of and protection by IFNs has been reported, including B. anthracis in vitro. In vivo, we find that (1) the type I IFN inducer, Poly-ICLC, strongly and rapidly protects mice; (2) the protection is IFN-mediated since recombinant murine IFN-beta can protect, and protection by Poly-ICLC is abrogated in IFN type I receptor knockout mice. The greatest protection by Poly-ICLC was conferred by intranasal treatment. A delay in death was observed with the intramuscular route alone, but was not significant. Together, the results suggest the IFN defense could protect mice, up to 60%, against lethal inhalational anthrax, and thus have important medical implications for therapy of human anthrax.

Figures

FIG. 1.

Poly-ICLC protects mice infected with anthrax spores. Protection of mice by Poly-ICLC (25 μg) given both intramuscularly and intranasally 24 h prior to lethal inhalational anthrax exposure. *Indicates significance from control by Fisher Exact test (p < 0.05).

FIG. 2.

Type I IFN rMulFNβ delays death in mice infected with anthrax spores. Delay in death of Swiss Webster mice when rMuIFNβ is given intraperitoneally 24 h prior to lethal inhalational anthrax exposure. *Indicates significance from control by Fisher Exact test (p < 0.05).

FIG. 3.

Inhalation anthrax is more severe in type I receptor knockout (KO) mice. Type I interferon receptor KO mice have a more severe infection and are not protected by Poly-ICLC compared to wild-type 129S mice. *Indicates significance from the control by Fisher Exact Test (p < 0.05).

FIG. 4.

Intranasal administration of Poly-ICLC protects mice infected with anthrax spores better than intraperitoneal and intramuscular routes. Intranasal Poly-ICLC (25 μg) given 24 h prior to lethal inhalational anthrax exposure offers better protection than intramuscular and intraperitoneal administration. *Indicates significance from control by Fisher Exact test (p < 0.05).

FIG. 5.

Intraperitoneal administration of Poly-ICLC eliminates the protective effects of intranasal administration of Poly-ICLC. Intraperitoneal administration of Poly-ICLC (25 μg) given 24 h prior to lethal inhalational anthrax offers no protective effects against inhalational anthrax and eliminates the protective effects of the intranasal dose (25 μg) when combined. *Indicates significance from control by Fisher Exact test (p < 0.05).