IL-13 pre-treatment of murine peritoneal macrophages increases their anti-Toxoplasma gondii activity induced by lipopolysaccharides.
Th1 cytokines and microbial lipopolysaccharides (LPS) activate macrophages to produce inflammatory mediators and effector molecules. Althrough Th2 cytokines often have an opposite action to Th1 cytokines and down-modulate the inflammatory response of macrophages, they can induce a distinct alternative activation that is beneficial in host defence. In this study, we report that IL-13 enhances the anti-Toxoplasma activity of LPS-activated murine macrophages. The inhibition of parasite proliferation was not related to reduced Toxoplasma gondii penetration into the cells, nor to the conversion of tachyzoites into bradyzoites. Used alone, IL-13 triggers the polarisation of macrophages towards type 2. However, in LPS-activated macrophages, we show the priming capacity of this cytokine to enhance the expression of inducible nitric oxide synthase (iNOS), a major marker of type 1 macrophages. This effect of IL-13 was not dependent on the activation state of macrophages (resident versus thioglycolate-elicited) or the timing of pre-treatment. We demonstrate a correlation between the enhancement of NO production and upgrading of the microbicidal effectiveness of the macrophages. Thus, both Th2 and Th1 cytokines could activate macrophages to control infections.
Authier
Hélène
H
Laboratoire des macrophages, Médiateurs de l'Inflammation et Interactions Cellulaires, Université Paul Sabatier Toulouse III, EA2405, INSERM IFR31 BP84225, 31432 Toulouse Cedex 4, France.
Cassaing
Sophie
S
Bans
Valérie
V
Batigne
Philippe
P
Bessières
Marie-Hélène
MH
Pipy
Bernard
B
D000818:Animals; D001119:Arginase / Q000032:analysis / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D018793:Interleukin-13 / Q000494:pharmacology*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018793:Interleukin-13; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D001119:Arginase