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The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3 Yrs to >70 Yrs ). A broad increase in serum soluble mediators was observed at 6-10 Yrs with subsequent decline at 11-20 Yrs and 21-30 Yrs followed by a second round of upregulation starting at 31-40 Yrs , with a large increase at 51-60 Yrs and a marked decline at age >70 Yrs . Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6-10 Yrs and a second wave around 61-70 Yrs . A universal decline was observed later at age >70 Yrs . In males, the second wave started earlier at 31-40 Yrs with a peak at 51-60 Yrs and a further smooth decline towards >70 Yrs . Conversely, in females, the first peak extended from 3-5 Yrs to 6-10 Yrs and the second wave starting around 41-50 Yrs with a peak at 61-70 Yrs followed by a sharp decline at >70 Yrs . Overall, CCL11, CXCL8, IL-1β, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31-40 Yrs ) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3-5 Yrs , with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11-20 Yrs , 51-60 Yrs and >70 Yrs ) than in males (at 21-30 Yrs , 61-70 Yrs ). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes., (Copyright © 2022. Published by Elsevier Inc.)

Background: Toxoplasma gondii is a protozoan parasite that causes congenital toxoplasmosis by transplacental transmission. Parasite strains are genetically diverse and disease severity is related to the genotype. In Uberlândia city, Brazil, two virulent strains were isolated: TgChBrUD1 and TgChBrUD2. Congenital toxoplasmosis is more prevalent in South America compared to Europe, and more often associated with severe symptoms, usually as a result of infection with atypical strains., Methods: Considering that T. gondii has shown high genetic diversity in Brazil, the effectiveness of traditional treatment may not be the same, as more virulent strains of atypical genotypes may predominate. Thus, the aim of this study were to evaluate the Brazilian strain infection rate in human villous explants and the azithromycin efficacy with regard to the control of these strains compared to traditional therapy. Villi were infected with RH, ME49, TgChBrUD1 or TgChBrUD2 strains and treated with azithromycin, spiramycin or a combination of pyrimethamine plus sulfadiazine. The villous viability was analyzed by LDH assay and morphological analysis. Parasite proliferation, as well as production of cytokines was analyzed by qPCR and ELISA, respectively. Statistical analysis was performed using the GraphPad Prism 5.0., Results: The treatments were not toxic and TgChBrUD1 infected villi showed a higher parasite burden compared with others strains. Treatments significantly reduced the intracellular proliferation of T. gondii, regardless of the strain. TgChBrUD1-infected villi produced a larger amount of MIF, IL-6 and TGF-β1 compared with other infected villi. Azithromycin treatment increased MIF production by RH- or TgChBrUD2-infected villi, but in ME49- or TgChBrUD1-infected villi, the MIF production was not altered by treatment. On the other hand, azithromycin treatment induced lower IL-6 production by ME49- or TgChBrUD1-infected villi., Conclusions: Azithromycin treatment was effective against T. gondii Brazilian strains compared with conventional treatment. Also, the TgChBrUD1 strain replicated more in villi and modulated important cytokines involved in parasite control, showing that different strains use different strategies to evade the host immune response and ensure their survival.

The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)