African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia

N A Mabbott; P S Coulson; L E Smythies; R A Wilson; J M Sternberg

African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia

N A Mabbott, P S Coulson, L E Smythies, R A Wilson, J M Sternberg

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.

Original language	English
Pages (from-to)	476-480
Number of pages	5
Journal	Immunology
Volume	94
Issue number	4
Publication status	Published - Aug 1998

Keywords

VARIANT SURFACE GLYCOPROTEIN
BRUCEI INFECTION
IN-VIVO
MACROPHAGES
INHIBITION
GENERATION
INDUCTION
SYNTHASE
ANTIGEN
GROWTH

Cite this

@article{4362e0adbe3e47338746cae6f67e52f4,

title = "African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia",

abstract = "Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.",

keywords = "VARIANT SURFACE GLYCOPROTEIN, BRUCEI INFECTION, IN-VIVO, MACROPHAGES, INHIBITION, GENERATION, INDUCTION, SYNTHASE, ANTIGEN, GROWTH",

author = "Mabbott, {N A} and Coulson, {P S} and Smythies, {L E} and Wilson, {R A} and Sternberg, {J M}",

year = "1998",

month = aug,

language = "English",

volume = "94",

pages = "476--480",

journal = "Immunology",

issn = "0019-2805",

publisher = "Wiley-Blackwell",

number = "4",

}

African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia. / Mabbott, N A; Coulson, P S; Smythies, L E et al.

In: Immunology, Vol. 94, No. 4, 08.1998, p. 476-480.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia

AU - Mabbott, N A

AU - Coulson, P S

AU - Smythies, L E

AU - Wilson, R A

AU - Sternberg, J M

PY - 1998/8

Y1 - 1998/8

N2 - Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.

AB - Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.

KW - VARIANT SURFACE GLYCOPROTEIN

KW - BRUCEI INFECTION

KW - IN-VIVO

KW - MACROPHAGES

KW - INHIBITION

KW - GENERATION

KW - INDUCTION

KW - SYNTHASE

KW - ANTIGEN

KW - GROWTH

M3 - Article

VL - 94

SP - 476

EP - 480

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 4

ER -