Inducible nitric oxide synthase and arginase expression in heart tissue during acute Trypanosoma cruzi infection in mice: arginase I is expressed in infiltrating CD68+ macrophages.
In Chagas disease, which is caused by Trypanosoma cruzi, macrophages and cardiomyocytes are the main targets of infection. Classical activation of macrophages during infection is protective, whereas alternative activation of macrophages is involved in the survival of host cells and parasites. We studied the expression of inducible nitric oxide synthase (iNOS) and arginase as markers of classical and alternative activation, respectively, in heart tissue during in vivo infection of BALB/c and C57BL/6 mice. We found that expression of arginase I and II, as well as that of ornithine decarboxylase, was much higher in BALB/c mice than in C57BL/6 mice and that it was associated with the parasite burden in heart tissue. iNOS and arginase II were expressed by cardiomyocytes. Interestingly, heart-infiltrated CD68+ macrophages were the major cell type expressing arginase I. T helper (Th) 1 and Th2 cytokines were expressed in heart tissue in both infected mouse strains; however, at the peak of parasite infection, the balance between Th1 and Th2 predominantly favored Th1 in C57BL/6 mice and Th2 in BALB/c mice. The results of the present study suggest that Th2 cytokines induce arginase expression, which may influence host and parasite cell survival but which might also down-regulate the counterproductive effects triggered by iNOS in the heart during infection.
Cuervo
Henar
H
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Autónoma de Madrid (UAM), Cantoblanco, Madrid, Spain.
Pineda
Miguel A
MA
Aoki
M Pilar
MP
Gea
Susana
S
Fresno
Manuel
M
Gironès
Núria
N
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D014355:Chagas Disease / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D032383:Myocytes, Cardiac / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D013047:Specific Pathogen-Free Organisms; D014349:Trypanosoma cruzi; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001119:Arginase; D002352:Carrier Proteins; D016207:Cytokines; D019746:Intramolecular Oxidoreductases; D052247:Nitric Oxide Synthase Type II; D000071876:Prostaglandin-E Synthases; C081026:CD68 protein, mouse; D000097382:CD68 Molecule