A novel and divergent role of granzyme A and B in resistance to helminth infection.
Granzyme (gzm) A and B, proteases of NK cells and T killer cells, mediate cell death, but also cleave extracellular matrices, inactivate intracellular pathogens, and induce cytokines. Moreover, macrophages, Th2 cells, regulatory T cells, mast cells, and B cells can express gzms. We recently reported gzm induction in human filarial infection. In this study, we show that in rodent filarial infection with Litomosoides sigmodontis, worm loads were significantly reduced in gzmA × B and gzmB knockout mice during the whole course of infection, but enhanced only early in gzmA knockout compared with wild-type mice. GzmA/B deficiency was associated with a defense-promoting Th2 cytokine and Ab shift, enhanced early inflammatory gene expression, and a trend of reduced alternatively activated macrophage induction, whereas gzmA deficiency was linked with reduced inflammation and a trend toward increased alternatively activated macrophages. This suggests a novel and divergent role for gzms in helminth infection, with gzmA contributing to resistance and gzmB promoting susceptibility.
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany.
Wiebke
W
Hartmann
Benjamin J
BJ
Marsland
Benjamin
B
Otto
Jens
J
Urny
Bernhard
B
Fleischer
Simone
S
Korten
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D005260:Female; D005368:Filariasis / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D005370:Filarioidea / Q000276:immunology*; D053804:Granzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007113:Immunity, Innate; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016205:Sigmodontinae; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D000909:Antibodies, Helminth; D053804:Granzymes