The Role of IFN-γ and Toll-Like Receptors in Nephropathy Induced by Toxoplasma gondii Infection

• Published in: Microbiology and immunology 2004-01, Vol.48 (8), p.617-628
• Main Authors: Kudo, Masamichi, Aosai, Fumie, Mun, Hye-Seong, Norose, Kazumi, Akira, Shizuo, Iwakura, Yoichiro, Yano, Akihiko
• Format: Article
• Language: English
• Subjects: Animals; Female; IFN-γ; Interferon-gamma - metabolism; kidney; Kidney Diseases - parasitology; Kidney Diseases - physiopathology; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; TLR family; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors; Toxoplasma - pathogenicity; Toxoplasma gondii; Toxoplasmosis, Animal - parasitology; Toxoplasmosis, Animal - physiopathology
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.2004.tb03559.x

The pathologic links between Toxoplasma gondii infections and renal diseases have not yet been established. Gamma interferon (IFN‐γ) and Toll‐like receptors (TLRs) are involved in the host defense mechanism against T. gondii infection. The role of IFN‐γ and TLRs in renal function of T. gondii‐infected mice was studied using wild type (WT), TLR2‐deficient and TLR4‐deficient mice perorally infected with cysts of an avirulent cyst‐forming Fukaya strain of T. gondii. T. gondii was abundant in kidneys in IFN‐γ KO (GKO) mice as determined by a quantitative competitive‐polymerase chain reaction (QC‐PCR). But, T. gondii was not detected in kidneys in WT, TLR2‐deficient and TLR4‐deficient mice. Interestingly, renal function of TLR2‐deficient and TLR4‐deficient mice was damaged as evaluated by serum creatinine, serum blood urea nitrogen (BUN), and urine albumin/creatinine ratio (ACR), whereas renal function of GKO and WT mice was not damaged. Histopathology of TLR2‐deficient mice exhibited glomerular and extracellular matrix swelling with advancing glomerular tissue proliferation, thickened Bowman's capsules and vacuolization of tubules. Renal immunofluorescence study of T. gondii‐infected TLR2‐deficient mice displayed positive staining of the glomerular basement membrane, mesangial areas and peritubular capillaries. The damage of kidney from TLR4‐deficient mice was less severe compared to TLR2‐deficient mice, and histopathological damage of kidney was not observed in WT and GKO mice. These results indicate that TLR2, but not IFN‐γ, plays a role in the protection of the renal function against T. gondii infection.