IFN inhibits inflammatory responses and protective immunity in mice infected with the nematode parasite, Nippostrongylus brasiliensis.
Mice infected with the gastrointestinal nematode parasite Nippostrongylus brasiliensis (Nb) develop responses associated with enhanced production of IL-4 (increased serum IgE levels and intestinal mucosal mastocytosis) and IL-5 (tissue and peripheral blood eosinophilia). The antagonistic effects of IFN on IL-4-mediated responses prompted an examination of the effects of IFN on the host response to Nb. Treatment with rIFN-alpha and rIFN-gamma induced a marked increase in parasite egg production (fecundity) in BALB/c mice infected with Nb and delayed intestinal expulsion of adult worms. Treatment with rIFN-alpha or rIFN-gamma also inhibited the rise in peripheral blood eosinophilia that follows inoculation with Nb, and the intensity of pulmonary perivascular tissue eosinophilia. However, Nb-induced increases in serum IgG levels and intestinal mastocytosis were only temporarily delayed by IFN. Induction of endogenous IFN production by injection of fixed Brucella abortus into mice infected with Nb also resulted in an increased worm fecundity and delayed adult worm expulsion. These effects were ablated when mice given Brucella abortus also received injections of neutralizing anti-IFN antibodies. Thus, IFN inhibit host protective immunity to Nb, perhaps by interfering with the production and effects of Th2 cytokines.
Urban
J F
JF
Helminthic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705.
Madden
K B
KB
Cheever
A W
AW
Trotta
P P
PP
Katona
I M
IM
Finkelman
F D
FD
D000818:Animals; D002003:Brucella abortus / Q000276:immunology; D004802:Eosinophilia / Q000209:etiology / Q000517:prevention & control; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D008415:Mastocytosis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology / Q000302:isolation & purification; D011994:Recombinant Proteins; D017206:Strongylida Infections / Q000209:etiology / Q000276:immunology* / Q000469:parasitology
D007369:Interferon Inducers; D007370:Interferon Type I; D015848:Interleukin-5; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma