TRAF6 signaling in T cells is crucial for the pathogenicity of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an incurable chronic autoimmune disease affecting the central nervous system (CNS). Although IL-17-producing helper T (Th17) cells are thought to be one of the exacerbating factors in MS, the underlying pathogenic mechanism is incompletely understood. TNF receptor-associated factor 6 (TRAF6) deficient T cells exhibited enhanced Th17 cell differentiation, however, the physiological relevance of TRAF6 in T cells remains unknown. Here, we induced experimental autoimmune encephalomyelitis (EAE) in T cell-specific TRAF6 deficient (TRAF6ΔT) mice to investigate the role of TRAF6 in T cells during the course of MS using an EAE model. Although Th17 cell differentiation was enhanced in TRAF6ΔT mice, mutant mice were resistant to EAE. In contrast, TRAF6 loss did not affect regulatory T-cell differentiation. Consistent with the severity of EAE, a small number of infiltrating T cells and a small area of demyelination were observed in the CNS of TRAF6ΔT mice. Moreover, myelin oligodendrocyte glycoprotein-induced IL-17 production in TRAF6-deficient T cells was significantly suppressed. We further confirmed lower levels of CD69 and granulocyte-macrophage colony-stimulating factor in Th17 cells of TRAF6ΔT mice than in wild-type mice. In contrast, the expression of IL-10 and cytotoxic T-lymphocyte-associated protein 4 in T cells was significantly elevated in the absence of TRAF6 because of enhanced T-cell receptor signaling. Collectively, TRAF6 signaling in T cells contributes to the pathogenesis of EAE by regulating the pathogenicity and autoantigen reactivity of Th17 cells.

CCR2-dependent placental migration of inflammatory monocytes suppresses abnormal pregnancies caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gongii) is a zoonotic protozoan parasite that causes congenital toxoplasmosis, including fetal death, abortion, stillbirth, morphological abnormalities, and premature birth. Primary T. gondii infection in pregnant women results in congenital toxoplasmosis. C-C chemokine receptor (CCR) 2 is reportedly a critical host defense factor against T. gondii infection. However, details of the role of CCR2 in the host immune response to T. gondii in congenital toxoplasmosis remain unclear. Here, we infected pregnant CCR2-deficient mice with T. gondii, resulting in stillbirth, embryonic resorption, fetal morphological abnormalities, and preterm delivery at significantly higher rates than those in pregnant wild-type mice. Consistent with the severity of abnormal pregnancy, a large area of placental hemorrhage and a large number of T. gondii infections around the hemorrhagic area were observed in the placentas of CCR2-deficient mice. In addition, the accumulation of inflammatory monocytes in the placenta was reduced in CCR2-deficient mice during infection. We further confirmed that the adoptive transfer of inflammatory monocytes collected from wild-type mice into T. gondii-infected pregnant CCR2-deficient mice effectively suppressed placental damage and abnormal pregnancy. Collectively, CCR2 contributes to pregnancy maintenance by regulating the migration of inflammatory monocytes into the placenta of T. gondii-infected pregnant mice.

Tapeworm Infection Diagnosed after Campylobacter jejuni-induced Enteritis.

A 35-year-old man with fever and diarrhea visited our hospital because of white string-like fecal excretion. Based on a morphological examination of the excreted object, a Diphyllobothrium infection was suspected. Additionally, Gram staining of a fecal sample revealed Campylobacter infection. After the intraduodenal administration of meglumine/diatrizoate sodium, the tapeworm was excreted. A polymerase chain reaction-based DNA sequence analysis demonstrated that the tapeworm excreted in this case was Diphyllobothrium nihonkaiensis. This report presents a rare case of coinfection with Diphyllobothrium nihonkaiensis and Campylobacter jejuni. Therefore, it is important to consider the coexistence of other intestinal infections when diagnosing parasitic infections in patients with fever.