Role of innate immune cells in protection against Toxoplasma gondii at inflamed site.
The intraperitoneal infection with Toxoplasma gondii (T. gondii) caused accumulation of gamma delta T, NK, NK1.1+T-like (NKT) cells at inflamed sites. To clarify the roles of these cells in protection against T. gondii at the inflamed sites, BALB/c mice were depleted of gamma delta T, NK, NK and NKT cells by treatment with antibody against TCR-gamma delta, asialoGM1 or Interleukin-2 receptor beta-chain (IL-2 R beta), respectively, prior to infection. Mice treated with anti-TCR-gamma delta monoclonal antibody (mAb) became more susceptible to infection, whereas mice treated with anti-IL-2R beta mAb acquired resistance. Treatment with anti-asialoGM1 Ab showed no effect. We previously reported that heat shock protein 65 (HSP65) in macrophages induced by gamma delta T cells plays an essential role in protective immunity against T. gondii infection, by preventing apoptotic death of infected macrophages. In the present study, we showed that treatment with anti-IL-2R beta mAb, but not with anti-asialoGM1 Ab, enhanced the HSP65 induction in macrophages, and inhibited Interleukin-4 (IL-4) expression in nonadherent peritoneal exudate cells. Furthermore, neutralization of endogenous IL-4 by anti-IL-4 mAb enhanced the HSP65 induction in macrophages. These findings suggest that NKT cells, but not NK cells, negatively regulate the protective immunity against T. gondii infection possibly by producing IL-4 and suppressing HSP65 induction.
Nakano
Y
Y
Department of Parasitology and Immunology, University of Tokushima School of Medicine, Tokushima, Japan.
Hisaeda
H
H
Sakai
T
T
Zhang
M
M
Maekawa
Y
Y
Zhang
T
T
Himeno
K
K
D000818:Animals; D000918:Antibody Specificity; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D015870:Gene Expression; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010529:Peritoneal Cavity; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology*
D001426:Bacterial Proteins; D018834:Chaperonin 60; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; C074119:heat-shock protein 65, Mycobacterium; D015847:Interleukin-4; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma; D018833:Chaperonins