Human and rodent interferon‐γ as a growth factor for Trypanosoma brucei

Abstract

An example for the bidirectional exchange of activating signals between a pathogen and immunocompetent cells in the host is presented. Trypanosoma brucei, which include subspecies that cause African sleeping sickness, secrete a molecule that triggers lymphocytes to produce interferon (IFN)-gamma. We now report that proliferation of T. brucei is stimulated in axenic cultures by IFN-gamma. The growth-enhancing effect on the pathogen is inhibited by anti-IFN-gamma receptor (R) antibodies and does not occur after exposure to other cytokines, i.e. IFN-alpha, IFN-beta and tumor necrosis factor (TNF)-alpha. While rodent-pathogenic T. brucei strains are stimulated by rat IFN-gamma, human pathogenic strains are more potently stimulated by human IFN-gamma. Rat and human IFN-gamma can partially block each others effects. Mice with disrupted IFN-gamma genes have reduced parasitemia and prolonged survival, while the outcome is reversed in mice that lack the IFN-gamma R gene.

Interferon‐γ and Interleukin‐12 Genes are Preferentially Expressed During Early Experimental African Trypanosomiasis and Suppressed by Denervation of the Spleen

“…Other studies have documented that the IFN-␥ mRNA expression is correlated closely with the protein production [24,25]. IFN-␥ can be stimulated by both intracellular [26] and extracellular parasites [4], and has been considered as an important element in the host parasite interactions. In the case of African trypanosomiasis, the IFN-␥ constitutes a parasite growth stimulator, and has critical effects on the outcome of the disease [4].…”

“…IFN-␥ can be stimulated by both intracellular [26] and extracellular parasites [4], and has been considered as an important element in the host parasite interactions. In the case of African trypanosomiasis, the IFN-␥ constitutes a parasite growth stimulator, and has critical effects on the outcome of the disease [4]. The IL-12 mRNA expression was significantly elevated in the early infection and was reduced after a splenic 4.…”

“…Experimental African trypanosomiasis was established in rats and mice to study immunopathogenetic mechanisms during the disease. Several studies showed early production of interferon (IFN)-␥ in the spleen (12 h after infection) and demonstrated critical interactions between IFN-␥ and CD8 þ T cells [3,4]. The non major histocompatibility complex (MHC) gene related and CD8…”

“…It was also suggested that the TGF-␤ and the tumour necrosis factor (TNF)-␤ might contribute to the immunosuppression, which is a major feature of African trypanosomiasis [5]. As IFN-␥ has been described as a growth-promoting molecule for the parasites [4], tumour necrosis factor (TNF)-␣ was associated with their lysis [6]. Thus, the account of cytokines to this infection is still unclear and requires more deep investigations to better understanding of the immunological events during the disease.…”

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

“…Other factors include the pH of the blood, immune responses including hydrolysis products of cAMP analogs (40), a specific induction signal [stumpy induction factor (SIF)] (41), and changes in the cytokine(s) and chemokine(s) activity of the host (42). Earlier research also shows that mammalian growth factors like EGF and other factors may influence trypanosome growth and differentiation in the host (43)(44)(45)(46)(47) although the lack of an identifiable EGF receptor gene sequence in the T. brucei genome suggests a form of molecular mimicry (48). Accumulative studies indicate, although it has not been fully established yet, that the growth and differentiation of the single-cell T. brucei is, at least partly, under external control and that communication between parasite-parasite and parasite-host may be occurring.…”