TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection

Abstract

To investigate the role of the Toll-like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2-, TLR4- and MyD88-deficient mice with the avirulent cyst-forming Fukaya strain of T. gondii. All TLR2- and MyD88-deficient mice died within 8 days, whereas all TLR4-deficient and wild-type mice survived after i.p. infection with a high dose of T. gondii. Peritoneal macrophages from T. gondii-infected TLR2- and MyD88-deficient mice did not produce any detectable levels of NO. T. gondii loads in the brain tissues of TLR2- and MyD88-deficient mice were higher than in those of TLR4-deficient and wild-type mice. Furthermore, high levels of IFN-gamma and IL-12 were produced in peritoneal exudate cells (PEC) of TLR4-deficient and wild-type mice after infection, but low levels of cytokines were produced in PEC of TLR2- and MyD88-deficient mice. On the other hand, high levels of IL-4 and IL-10 were produced in PEC of TLR2- and MyD88-deficient mice after infection, but low levels of cytokines were produced in PEC of TLR4-deficient and wild-type mice. The most remarkable histological changes with infiltration of inflammatory cells were observed in lungs of TLR2-deficient mice infected with T. gondii, where severe interstitial pneumonia occurred and abundant T. gondii were found.

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

“…The critical role of TLR2 and TLR-linked cytoplasmic adapter protein, MyD88, against extracellular gram-positive bacteria has been shown in mice blood and kidney (4,36). Recently, we showed the importance of TLR2 (26) and MyD88 (7) for protective immunity to T. gondii infection. Consistent with these reports, the present study has demonstrated the renal dysfunction and histopathological damage following T. gondii infection in TLR2-deficient mice.…”

“…Renal inflammation markedly enhances synthesis of TLR2 and TLR4 mRNA in renal tubular epithelial cells (40). Recently, we revealed that MyD88 and TLR2 play a protective role against T. gondii infection (7,26).…”

Production of IL-12 by Macrophages Infected withToxoplasma gondiiDepends on the Parasite Genotype

“…Glycophosphatidylinositol anchors and glycoinositolphospholipids from the protozoan parasite Trypanosoma cruzi (31), as well as lipopeptides/glycolipids from Mycoplasma spp (45) and Mycobacteria tuberculosis (46), have been shown to trigger inflammatory cytokine production by signaling via TLR2. Moreover, a role for TLR2 has been implicated in resistance to in vivo challenge with high numbers of oocysts from an avirulent strain of T. gondii (47). In addition to signaling in response to LPS, TLR4 has been implicated in the binding of ligands that are produced in response to cellular injury, such as murine heat shock protein 70 and components of the extracellular matrix (19).…”

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…Their ligands induce the production of inflammatory chemokines and cytokines (that is, CCL3, CCL5, interleukin (IL)-6, IL-8 and IL-12) that mediate recruitment of professional phagocytes and dendritic cells. [8][9][10] Crucial adaptative responses include CD8 þ cytotoxicity of infected cells, antibody-mediated phagocytosis and NK cell antibody-mediated cytotoxicity (NK-ADCC). A T helper 1 (Th1) profile (that is, IL-12 and interferon-g (IFN-g)) is essential to induce these mechanisms.…”