WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production.
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-gamma 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-alpha, 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.
Hamano
Shinjiro
S
The Department of Parasitology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Himeno
Kunisuke
K
Miyazaki
Yoshiyuki
Y
Ishii
Kazunari
K
Yamanaka
Atsushi
A
Takeda
Atsunobu
A
Zhang
Manxin
M
Hisaeda
Hajime
H
Mak
Tak W
TW
Yoshimura
Akihiko
A
Yoshida
Hiroki
H
D000818:Animals; D001769:Blood / Q000382:microbiology; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000378:metabolism*; D018123:Receptors, Interleukin; D013154:Spleen / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014349:Trypanosoma cruzi
D016207:Cytokines; C484747:Il27ra protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin