title: Differential effects of Trypanosoma brucei gambiense and Trypanosoma brucei brucei on rat macrophages.
abstract: Mammalian immune responses to Trypanosoma brucei infection are important to control of the disease. In rats infected with T. brucei gambiense (Wellcome strain; WS) or T. brucei brucei (interleukin-tat 1.4 strain [ILS]), a marked increase in the number of macrophages in the spleen can be observed. However, the functional repercussions related to this expansion are not known. To help uncover the functional significance of macrophages in the context of trypanosome infection, we determined the mRNA levels of genes associated with an increase in macrophage number or macrophage function in WS- and ILS-infected rats and in cultured cells. Specifically, we assayed mRNA levels for macrophage colony stimulating factor (M-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and macrophage migration inhibitory factor (MIF). Upregulation of GM-CSF and MIF mRNA levels was robust in comparison with changes in M-CSF levels in ILS-infected rats. By contrast, upregulation of M-CSF was more robust in WS-infected rats. The phagocytic activity in macrophages harvested from ILS-infected rat spleens, but not WS-infected spleens, was higher than that in macrophages from uninfected rats. These results suggest that macrophages of WS-infected rats change to an immunosuppressive type. However, when WS or ILS is cocultured with spleen macrophages or HS-P cells, a cell line of rat macrophage origin, M-CSF is upregulated relative to GM-CSF and MIF in both cell types. Anemia occurs in ILS-, but not WS-infected, rats. Treatment of spleen macrophages or HS-P cells cocultured with ILS with cobalt chloride, which mimics the effects of anemia-induced hypoxia, led to downregulation of M-CSF mRNA levels, upregulation of GM-CSF and MIF, and an increase in phagocytic activity. However, the effect of cobalt chloride on spleen macrophages and HS-P cells cocultured with WS was restricted. These results suggest that anemia-induced hypoxia in ILS-infected rats stimulates the immune system and activates macrophages.
authors.affiliation: Laboratory of Bioenvironmental Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan. nisimura@vet.osakafu-u.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishimura
authors.forename: Haruna
authors.initials: H
authors.lastname: Nakaya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Saburo
authors.initials: S
authors.lastname: Matsuo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D008297:Male; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010587:Phagocytosis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D014346:Trypanosoma brucei brucei / Q000502:physiology*; D014347:Trypanosoma brucei gambiense / Q000502:physiology*; D014353:Trypanosomiasis, African / Q000276:immunology / Q000469:parasitology
chemical_list: D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor