Nervous system‐related tropism of SARS‐CoV‐2 and autoimmunity in COVID‐19 infection

European Journal of Immunology, Год журнала: 2023, Номер 54(1)

Опубликована: Сен. 21, 2023

The effects of SARS-CoV-2 in COVID-19 on the nervous system are incompletely understood. can infect endothelial cells, neurons, astrocytes, and oligodendrocytes with consequences for host. There indications that infection these CNS-resident cells may result long-term effects, including emergence neurodegenerative diseases. Indirect relate to induction autoimmune disease involving molecular mimicry or/and bystander activation T- B autoantibodies against various self-antigens. Data obtained preclinical models coronavirus-induced gives important clues understanding system-related assault SARS-CoV-2. pathophysiology long-COVID syndrome post-COVID which autoimmunity immune dysregulation might be driving forces still A better nervous-system-related immunity support development therapeutic approaches. In this review, current tropism system, associated responses, diseases summarized. data indicates there is viral resulting conditions. Prevention by means vaccination currently best strategy prevention subsequent tissue damage system.

Язык: Английский

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An AMBRA1, ULK1 and PP2A regulatory network regulates cytotoxic T cell differentiation via TFEB activation

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Дек. 30, 2024

The scaffold protein AMBRA1, which participates in the autophagy pathway, also promotes CD4

Язык: Английский

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Polo-like kinase 1 regulates immune synapse assembly and cytotoxic T cell function by driving microtubule dynamics

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 13, 2023

Abstract Elimination of virally infected or tumoral cells is mediated by cytotoxic T (CTL). Upon antigen recognition CTLs assemble a specialized signaling and secretory domain at the interface with their target, immune synapse (IS). During IS formation acquire transient polarity, marked re-orientation centrosome microtubule cytoskeleton toward IS, thus directing transport delivery lytic granules to target cell. Based on implication kinase Aurora-A in CTL function we hypothesized that its substrate, mitotic regulator Polo-like 1 (PLK1), may participate assembly. We demonstrate PLK1 phosphorylated upon TCR triggering polarizes IS. silencing inhibition results impaired assembly function, as witnessed defective synaptic accumulation TCRs well compromised granule polarization resulting cell killing. This achieved coupling early dynamics, pivotal for CTL-mediated cytotoxicity. These identify new player function. Summary statement The promotes dynamics

Язык: Английский

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Pandemic preparedness through genomic surveillance: Overview of mutations in SARS-CoV-2 over the course of COVID-19 outbreak

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 14, 2023

ABSTRACT Genomic surveillance is a vital strategy for preparedness against the spread of infectious diseases and to aid in development new treatments. In an unprecedented effort, millions samples from COVID-19 patients have been sequenced worldwide SARS-CoV-2. Using more than 8 million sequences that are currently available GenBank’s SARS-CoV-2 database, we report comprehensive overview mutations all 26 proteins open reading frames (ORFs) virus. The results indicate spike protein, NSP6, nucleocapsid envelope protein ORF7b shown highest mutational propensities so far (in order). particular, has rapid acceleration post-vaccination period. Monitoring rate non-synonymous (K ) provides fairly reliable signal genomic surveillance, successfully predicting surges 2022. Further, external (spike, membrane, envelope, proteins) show significant number compared NSPs. Interestingly, these four showed changes K typically 2 4 weeks before increase human infections (“surges”). Therefore, our analysis real time SARS-CoV-2, accessible through project website http://pandemics.okstate.edu/covid19/ . Based on ongoing mutation trends virus, predictions what likely mutate next also made possible by approach. proposed framework general thus applicable other pathogens. approach fully automated needed address fast-moving pandemic such as COVID-19.

Язык: Английский

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Leukemic cell-secreted interleukin-9 suppresses cytotoxic T cell-mediated killing in chronic lymphocytic leukemia

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 24, 2023

ABSTRACT The tumor microenvironment (TME) plays a central role in the pathogenesis of chronic lymphocytic leukemia (CLL), contributing to disease progression and chemoresistance. Leukemic cells shape TME into pro-survival immunosuppressive niche through contact-dependent contact-independent interactions with cellular components TME. Immune synapse (IS) formation is defective CLL. Here we asked whether soluble factors released by CLL contribute their protection from cytotoxic T cell (CTL)-mediated killing interfering this process. We found that healthy CTLs cultured media conditioned leukemic patients or Eμ-TCL1 mice upregulate exhaustion marker PD-1 become unable form functional ISs kill target cells. These defects were more pronounced when lacking p66Shc, proapoptotic adaptor whose deficiency has been implicated aggressiveness both mouse model. Multiplex ELISA assays showed secrete abnormally elevated amounts CCL22, CCL24, IL-9 IL-10, which are further upregulated absence p66Shc. Among these, IL-10 also overexpressed patients, where they inversely correlated residual Using neutralizing antibodies recombinant cytokines show IL-9, but not mediates enhancement expression suppression effector functions CTLs. Our results demonstrate secreted negatively modulates anti-tumor immune abilities CTLs, highlighting new suppressive mechanism novel potential therapeutical

Язык: Английский

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