Toxoplasma type II effector GRA15 has limited influence in vivo.

Toxoplasma gondii is an intracellular parasite that establishes a long-term infection in the brain of many warm-blooded hosts, including humans and rodents. Like all obligate intracellular microbes, Toxoplasma uses many effector proteins to manipulate the host cell to ensure parasite survival. While some of these effector proteins are universal to all Toxoplasma strains, some are polymorphic between Toxoplasma strains. One such polymorphic effector is GRA15. The gra15 allele carried by type II strains activates host NF-κB signaling, leading to the release of cytokines such as IL-12, TNF, and IL-1ß from immune cells infected with type II parasites. Prior work also suggested that GRA15 promotes early host control of parasites in vivo, but the effect of GRA15 on parasite persistence in the brain and the peripheral immune response has not been well defined. For this reason, we sought to address this gap by generating a new IIΔgra15 strain and comparing outcomes at 3 weeks post infection between WT and IIΔgra15 infected mice. We found that the brain parasite burden and the number of macrophages/microglia and T cells in the brain did not differ between WT and IIΔgra15 infected mice. In addition, while IIΔgra15 infected mice had a lower number and frequency of splenic M1-like macrophages and frequency of PD-1+ CTLA-4+ CD4+ T cells and NK cells compared to WT infected mice, the IFN-γ+ CD4 and CD8 T cell populations were equivalent. In summary, our results suggest that in vivo GRA15 may have a subtle effect on the peripheral immune response, but this effect is not strong enough to alter brain parasite burden or parenchymal immune cell number at 3 weeks post infection.

Thyroid Eye Disease: Pilot Study Comparison Between Patients in United States-Based and India-Based Practices.

PURPOSE: Thyroid eye disease (TED) phenotype varies by ethnicity/race and genetic/environmental factors. This study compared demographic and clinical characteristics of TED patients from the US and India. DESIGN: Observational pilot study . METHODS: Sixty-four patients with TED ages ≥18 years old with active disease (onset of symptoms ≤18 months or presenting clinical activity score (CAS) ≥4) were recruited between March and October 2021 from clinical practices in the United States (Philadelphia, PA) (n = 30) and India (Hyderabad, India) (n = 34). Data collection at baseline and 3 months included clinical measurements, thyroid disease history, and photographs. Ocular symptoms and quality of life data were obtained by phone interview. CAS was calculated using the standard 7-point scale. RESULTS: There was no statistically significant difference in age, TED duration, or smoking status between patient groups. Both groups had good vision, a low rate of optic neuropathy, and comparable exophthalmometry. US patients were predominantly female (86.7% [26/30]), with a history of hyperthyroidism (96% 29/30). In comparison, Indian patients were 52.9% (18/34, P = .004) female; underlying thyroid disease was distributed between hyperthyroidism (52%), hypothyroidism (17.6%) and euthyroid (9.7%). Mean (SD) CAS in the US cohort was double the score in the India cohort (4.2 (1.7) vs 1.65 (1.7), respectively) (P < .0001). However, patients at both sites experienced subjective symptoms of TED at a similar frequency. CONCLUSIONS: Observed differences in TED between US and Indian patients warrant further investigation to elucidate differences in pathogenesis, disease expression, or other factors that may influence TED in diverse populations.