Mouse strain susceptibility to trypanosome infection: an arginase-dependent effect.
We previously reported that macrophage arginase inhibits NO-dependent trypanosome killing in vitro and in vivo. BALB/c and C57BL/6 mice are known to be susceptible and resistant to trypanosome infection, respectively. Hence, we assessed the expression and the role of inducible NO synthase (iNOS) and arginase in these two mouse strains infected with Trypanosoma brucei brucei. Arginase I and arginase II mRNA expression was higher in macrophages from infected BALB/c compared with those from C57BL/6 mice, whereas iNOS mRNA was up-regulated at the same level in both phenotypes. Similarly, arginase activity was more important in macrophages from infected BALB/c vs infected C57BL/6 mice. Moreover, increase of arginase I and arginase II mRNA levels and of macrophage arginase activity was directly induced by trypanosomes, with a higher level in BALB/c compared with C57BL/6 mice. Neither iNOS expression nor NO production was stimulated by trypanosomes in vitro. The high level of arginase activity in T. brucei brucei-infected BALB/c macrophages strongly inhibited macrophage NO production, which in turn resulted in less trypanosome killing compared with C57BL/6 macrophages. NO generation and parasite killing were restored to the same level in BALB/c and C57BL/6 macrophages when arginase was specifically inhibited with N(omega)-hydroxy-nor-L-arginine. In conclusion, host arginase represents a marker of resistance/susceptibility to trypanosome infections.
Duleu
Sébastien
S
Laboratoire de Parasitologie, Université Victor Ségalen, Bordeaux, France.
Vincendeau
Philippe
P
Courtois
Pierrette
P
Semballa
Silla
S
Lagroye
Isabelle
I
Daulouède
Sylvie
S
Boucher
Jean-Luc
JL
Wilson
Keith T
KT
Veyret
Bernard
B
Gobert
Alain P
AP
D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004789:Enzyme Activation / Q000276:immunology; D004790:Enzyme Induction / Q000276:immunology; D007113:Immunity, Innate; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D013045:Species Specificity; D014346:Trypanosoma brucei brucei / Q000254:growth & development / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000201:enzymology* / Q000276:immunology* / Q000469:parasitology
D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C481673:Arg2 protein, mouse; D001119:Arginase