Human cytomegalovirus (CMV) is a widespread persistent herpes virus requiring lifelong immune surveillance to maintain latency. Such long-term interactions with the immune system may be associated with deleterious effects including immune exhaustion and senescence. Regarding the COVID-19 pandemic, we asked whether CMV-specific cellular and humoral activity could influence immune responses toward SARS-CoV-2 and/or disease severity. All adults with mild ( n = 15) and severe ( n = 14) COVID-19 were seropositive for anti-CMV IgG, but negative for IgM antibodies. Antibody titers did not correlate with COVID-19 severity. Six patients presented elevated frequencies of CMV-specific CD4 + and CD8 + T cells producing IFNγ, IL-17, and TNFα, designated as CMV high responders (hiT CMV). In comparison to low CMV responders, hiT CMV individuals exhibited higher frequencies of SARS-CoV-2-specific CD4 + IL-17 + and CD8 + IFNγ + , IL-17 + or TNFα + T cells. These results indicate that high frequencies of CMV-specific T cells may be associated with a SARS-CoV-2-reactive profile skewed toward Th17-dominated immunity. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00430-022-00758-1.
Background Doxorubicin (DOX) antineoplastic is considered the prototype of cardiotoxicity for inducing direct damage to the myocardium. Pharmacological blockage of Angiotensin (Ang) II action is one of the main strategies to manage DOX‐induced cardiomyopathy. The effects are also mediated by the activation of the Mas receptor (MasR)/Ang‐(1‐7) axis, which is the counter‐regulatory axis of Ang II. The modulation of MasR/Ang‐(1‐7) axis is Ang‐(1‐7) (agonist) and A779 (antagonist) and may be a potential strategy in the context of cardiotoxicity. Objective Evaluate the influence of pharmacological modulation of MasR/Ang‐(1‐7) axis on DOX‐induced cardiotoxicity in cardiomyoblast cells. Methods Murine cardiomyoblasts (H9c2) were treated with A779 (10μM) for 30′ followed by Ang‐(1‐7) (100nM) for 30′ previous to expose with 0.1μM and 0.35μM (IC50) of DOX for 24h. Cell viability (Neutral Red and Trypan Blue), cell death profile (Annexin/7AAD), DNA damage induction (Comet Assay) and mitochondrial membrane integrity (Rhodamine 123) were evaluated after treatment protocol. The experiments were performed in triplicate, and data were analyzed by ANOVA followed by Dunnet, considering p <0.05. Results MasR modulation did not prevent the reduction of viability of cardiomyoblasts by DOX, neither altered the pattern of cell death. Both concentrations of DOX induced DNA strand breaks (C: 27.5 ± 13.4; DOX 0.1μM: 53.5 ± 9.1; DOX IC50: 109.5 ± 17.6 U.A.). Pretreatment with peptides suggested a reduction of the frequency of nucleus damage (DOX 0.1μM + Ang‐(1‐7): 36.5 ± 6.3; DOX 0.1μM +A779: 36.5 ± 0.7 U.A.) only at 0.1 μM DOX concentration, while pretreatment with A779 or Ang‐(1‐7) preserved the mitochondrial membrane integrity. Conclusion Modulation by agonism or antagonism of MasR in H9c2 cells reduces the DNA damage and the mitochondrial integrity. These results seem to be independent of MasR modulation, pointing to the involvement of other receptors and their crosstalk. Support or Funding Information CAPES, CNPq and FAPICC/ICFUC
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