Open AccessMechanisms of interferon‐beta‐induced inhibition of T oxoplasma gondii growth in murine macrophages and embryonic fibroblasts: role of immunity‐related GTP ase M 1
Author(s) -
Mahmoud Motamed Elsayed,
Ui Fumiki,
Salman Doaa,
Nishimura Maki,
Nishikawa Yoshifumi
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12423
Subject(s) - biology , toxoplasma gondii , microbiology and biotechnology , macrophage , interferon , cytokine , interferon gamma , priming (agriculture) , chemokine , immune system , nitric oxide , immunology , in vitro , biochemistry , antibody , botany , germination , endocrinology
Summary The apical complex of T oxoplasma gondii enables it to invade virtually all nucleated cells in warm‐blooded animals, including humans, making it a parasite of global importance. Anti‐ T . gondii cellular defence mechanisms depend largely on interferon ( IFN )‐γ production by immune cells. However, the molecular mechanism of IFN ‐β‐mediated defence remains largely unclear. Here, mouse peritoneal macrophages and murine embryonic fibroblasts ( MEF s) primed with recombinant IFN ‐β and IFN ‐γ showed different pathways of activation. Treatment of these cells with IFN ‐β or IFN ‐γ inhibited T. gondii (type II PLK strain) growth. Priming macrophages with IFN ‐β had no effect on inflammatory cytokine expression, inducible nitric oxide synthase or indoleamine 2,3‐dioxygenase, nor did it have an effect on their metabolites, nitric oxide and kynurenine respectively. In contrast, IFN ‐γ stimulation was characterized by classical macrophage activation and T . gondii elimination. IFN ‐β activation recruited the immunity‐related GTP ase M 1 ( IRGM 1) to the parasitophorous vacuole in the macrophages and MEF s. Anti‐toxoplasma activities induced by IFN ‐β were significantly reduced after IRGM 1 knockdown in murine macrophages and in IRGM 1‐deficient MEF s. Thus, this study unravels an alternative pathway of macrophage activation by IFN ‐β and provides a mechanistic explanation for the contribution of IRGM 1 induced by IFN ‐β to the elimination of T . gondii .