CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge.

CD8+ T lymphocytes play an important role in controlling infections by intracellular pathogens. Chemokines and their receptors are crucial for the migration of CD8+ T-lymphocytes, which are the main IFNγ producers and cytotoxic effectors cells. Although the participation of chemokine ligands and receptors has been largely explored in viral infection, much less is known in infection by Trypanosoma cruzi, the causative agent of Chagas disease. After T. cruzi infection, CXCR3 chemokine receptor is highly expressed on the surface of CD8+ T-lymphocytes. Here, we hypothesized that CXCR3 is a key molecule for migration of parasite-specific CD8+ T-cells towards infected tissues, where they may play their effector activities. Using a model of induction of resistance to highly susceptible A/Sn mice using an ASP2-carrying DNA/adenovirus prime-boost strategy, we showed that CXCR3 expression was upregulated on CD8+ T-cells, which selectively migrated towards its ligands CXCL9 and CXCL10. Anti-CXCR3 administration reversed the vaccine-induced resistance to T. cruzi infection in a way associated with hampered cytotoxic activity and increased proapoptotic markers on the H2KK-restricted TEWETGQI-specific CD8+ T-cells. Furthermore, CXCR3 receptor critically guided TEWETGQI-specific effector CD8+ T-cells to the infected heart tissue that express CXCL9 and CXCL10. Overall, our study pointed CXCR3 and its ligands as key molecules to drive T. cruzi-specific effector CD8+ T-cells into the infected heart tissue. The unveiling of the process driving cell migration and colonization of infected tissues by pathogen-specific effector T-cells is a crucial requirement to the development of vaccine strategies.

Is perivitelline space morphology of the oocyte associated with pregnancy outcome in intracytoplasmic sperm injection cycles?

OBJECTIVE(S): To investigate the effect of perivitelline space (PVS) abnormalities on the outcomes of intracytoplasmic sperm injection (ICSI) cycles in which the entire cohort was affected. STUDY DESIGN: Data from 9752 oocytes obtained from 1151 ICSI cycles performed from June/2010 to August/2016 in a private university-affiliated IVF centre. Cycles were divided into four groups according to the presence or absence of PVS abnormalities: PVS-L group (cycles with the entire oocyte cohort affected by large PVS, n = 265), PVS-G group (cycles with the entire oocyte cohort affected by PVS granularity, n = 280), PVS-L + PVS-G group (cycles with the entire oocyte cohort affected by PVS-L and PVS-G, n = 204), and control group (cycles with the entire oocyte cohort free of PVS abnormalities, n = 402). The effect of PVS abnormalities on ICSI outcomes was assessed by GLM adjusted for potential confounders. RESULTS: Groups with PVS abnormalities presented substantially higher FSH/follicle (p < 0.001) and FSH/oocyte (p < 0.001) ratios, and lower numbers of follicles (p < 0.001), oocytes (p < 0.001) and embryos (p = 0.002) compared to the control group. PVS-L + PVS-G implantation (p = 0.044) and pregnancy (p = 0.004) rates were significantly lower than in cycles with isolated PVS abnormalities and controls. CONCLUSION(S): Cycles in which the entire oocyte cohort is affected by both large PVS and PVS granularity have compromised implantation and pregnancy rates.