TY - JOUR
T1 - WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production
AU - Hamano, Shinjiro
AU - Himeno, Kunisuke
AU - Miyazaki, Yoshiyuki
AU - Ishii, Kazunari
AU - Yamanaka, Atsushi
AU - Takeda, Atsunobu
AU - Zhang, Manxin
AU - Hisaeda, Hajime
AU - Mak, Tak W.
AU - Yoshimura, Akihiko
AU - Yoshida, Hiroki
N1 - Funding Information:
We thank Dr. Kazutoshi Hiyama, Sawako Muroi, Miyuki Sano, and Michiyo Takeuchi for animal husbandry and technical help; Dr. Christopher Hunter for comments; and members of “Project W” for helpful discussion. This study was supported in part by grants from the Ministry of Education, Science, Technology, Sports and Culture of Japan (to H.Y., S.H., K.H., and A.Y.), and from Kowa Life Science Foundation (to S.H.).
PY - 2003/11
Y1 - 2003/11
N2 - WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1 -/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-γ that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-α, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.
AB - WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1 -/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-γ that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-α, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.
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U2 - 10.1016/S1074-7613(03)00298-X
DO - 10.1016/S1074-7613(03)00298-X
M3 - Article
C2 - 14614853
AN - SCOPUS:10744221849
SN - 1074-7613
VL - 19
SP - 657
EP - 667
JO - Immunity
JF - Immunity
IS - 5
ER -
