Relationship between the production of interferon-α/β and interferon-γ during acute toxoplasmosis

Abstract

Acute toxoplasmosis was induced in mice, and interferon (IFN) production in serum and by spleen cells was evaluated during the infection period. Interferon was characterized by acid-treatment and anti-IFN-alpha/beta neutralization. In order to verify the correlation between the unusual aspects of the IFN production and the induction of immunosuppression, splenocyte mitogen responsiveness was investigated concomitantly to IFN synthesis. The activity of Toxoplasma-induced serum IFN-alpha/beta increased gradually throughout all post-infection days, but IFN-gamma was not detected in the systemic circulation at any time during the infection. It was also observed that IFN-alpha/beta production and the capacity to produce IFN-gamma by spleen cells were closely and inversely correlated. As the infection progressed, more IFN-alpha/beta was produced, and the ability of spleen cells to produce IFN-gamma decreased. The observation that Toxoplasma-infected mice were concomitantly immunosuppressed (as documented by mitogen unresponsiveness and defective IFN-gamma production) in direct correlation to IFN-alpha/beta production, suggests that such IFN-alpha/beta production is an important factor associated with acute toxoplasmosis-induced immunosuppression.

Subversion of innate and adaptive immune responses by Toxoplasma Gondii

“…IFN-α and IFN-β are predominantly produced by leucocytes and fibroblasts, respectively, although other cell types may also contribute. The increased amounts of IFN-α/β in sera from T. gondii-infected mice correlate with a reduced IFN-γ production and proliferation of splenocytes (Table 1; Diez et al 1989). This suggests that the production of IFN-α/β induced by T. gondii during acute infection is associated with parasite-induced immunosuppression.…”

“…These results provide clear evidence that IL-10-induced immunosuppression following infection with T. gondii is beneficial for both the parasite and the host and favours a stable parasite-host relationship. In addition to IL-10, TGF-β is an important deactivator of macrophages (Langermans et al 2001), the Khan et al 1995;Ellis Neyer et al 1997;Bermudez et al 1993;Langermans et al 2001;Hunter et al 1995 Deactivation of macrophages Independent of PGE2 Indirect Induction of TGF-β Reduced TNF-α production by macrophages; reduced IFN-γ production by NK cells Antagonizes IL-12 Indirect IFN-α/-β upregulation Reduced IFN-γ levels and splenocyte proliferation ND Indirect Diez et al 1989 Inhibition of TNF-α and IL-12 production ND not determined production of which is triggered after infection with T. gondii (Table 1; Bermudez et al 1993). It also inhibits the production of IFN-γ by NK cells (Hunter et al 1995) and may thus downregulate regulatory and effector functions of anti-Toxoplasma cellular immunity during acute toxoplasmosis (Table 1).…”

“…Infection of mice with T. gondii induces the secretion of IFN-α/β, i.e. type I interferons (Diez et al 1989) which are prominently involved in resistance against viral infections. IFN-α and IFN-β are predominantly produced by leucocytes and fibroblasts, respectively, although other cell types may also contribute.…”

Protozoan Parasites and Type I IFNs

“…In the mouse model, IFN-I can already be detected in the serum of T. gondii -infected animals during the acute phase (58–60); IFN-I levels gradually increase with the progression of the infection (60). IFN-I was also detected in the brain and spleen of infected mice (61).…”

Role of gamma interferon inToxoplasma gondii infection

“…As will be described below, with the use of MAB against IFN-7, Nathan et al (18) there was production of only low levels of IFN-7 which may be a manifestation of the immunosuppression present during acute toxoplasma infection (56). Furthermore, Diez et al (57) demonstrated that when normal mice were acutely infected with the RH strain of Toxoptasma gondii, as the disease progressed, there was a decline in production of IFN-7, a progressive decrease in the proliferative response of lymphocytes to mitogen and an increase in production of IFN-~13. They postulated that the production of IFN-~]3 might be an important factor associated with the immunosuppression seen in acute toxoplasma infection.…”