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Interleukin‐12 promotes a chronic intestinal nematode infection
Author(s) -
Bancroft Allison J.,
Else Kathryn J.,
Sypek Joseph P.,
Grencis Richard K.
Publication year - 1997
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830270410
Subject(s) - biology , immunology , immune system , interleukin 12 , cytokine , nippostrongylus brasiliensis , acquired immune system , interferon gamma , intracellular parasite , interleukin 10 , chronic infection , cytotoxic t cell , in vitro , biochemistry
Abstract Resistance and susceptibility to the intestinal parasite Trichuris muris has been shown to be due to a dominant T helper 2 (Th2) and a dominant Th1 response, respectively. The factors determining the initial polarization of the immune response remain largely unresolved, although the cytokine environment at the time of antigen presentation clearly plays an essential role. Interleukin (IL)‐12, a cytokine produced mainly by macrophages, dendritic cells, and other monocytes has been shown to be important in driving a strong Th1 response by stimulating the production of interferon (IFN)‐γ from natural killer and Th0 cells and therefore forms a link between the innate and adaptive immune system. IL‐12 has been shown to play an important role in resistance to a number of intracellular pathogens, including Listeria and Leishmania. It has also been proposed as an anti‐tumor agent and for use in the treatment of HIV. Conversely, IL‐12 has been shown to prolong the survival of Nippostrongylus brasiliensis and to accelerate autoimmunity. Our studies demonstrate that by driving a strong Th1 response, IL‐12 promotes chronic T. muris infection when given to normally resistant BALB/K mice. Parasite‐specific IgG2a, a Th1 parameter of infection, was greatly up‐regulated, whereas some Th2 parameters of infection were down‐regulated. IL‐12 treatment could be delayed until 1 week after infection had started and still promote a strong Th1 response. The actions of IL‐12 in promoting a chronic infection were IFN‐γ dependent as an anti‐IFN‐γ mAb abrogated the effects of IL‐12.