Online seminar by Doug Drevets on Thursday, April 8

Thursday April 01 2021 - Thursday April 08 2021

ErasmusMC - Dept. of Immunology


announcement for an online seminar by Doug Drevets, entitled: “Roles of miR-155 in brain inflammation during neuroinvasive bacterial infection".

This online seminar will take place on Thursday, April 8, at 16:00 hrs.Please register before Wednesday April 7 by e-mail to: secretariaat.immunologie@erasmusmc.nl

 

Virtual “Erasmus Immunology Lectures” 2021

Thursday, April 8, 2021, 16:00 hrs.
Dept. of Immunology


“Roles of miR-155 in brain inflammation during neuroinvasive bacterial infection"

Douglas A. Drevets

Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Brain inflammation is a primary cause of neurologic injury during aging, neurodegeneration, and brain infection but dampening inflammation and its downstream neurological dysfunction can be challenging. For example, corticosteroids are the mainstay of anti-inflammatory treatment in response to bacterial CNS infection. Some patients benefit from this treatment during acute illness, but corticosteroids have limited impact in many patient groups and on long-term cognitive outcomes, particularly in adults. Manipulating expression of certain microRNA (miR) has salutary effects in some models of sterile brain inflammation and viral CNS infection suggesting this approach could be used for reducing CNS inflammation triggered by bacterial infection. miR-155 is a poly-functional, non-coding RNA that is upregulated by NF-κB in response to TLR-signaling and to cytokines such as IFN-β, IFN-γ and TNF. In microglia, miR-155 is upregulated during M1-polarization and promotes inflammation, it is also required for optimal development of IFN-γ-secreting antigen-specific CD8+ T-cells after viral and bacterial infection. We hypothesized that blockade of miR-155 in vivo could be a useful anti-inflammatory strategy that does not severely depress host bactericidal mechanisms. To study this in a clinically relevant model, we induced neuroinvasive Listeria monocytogenes (Lm) infection in mice via systemic injection, then treated the animals with the same antibiotic used for human listeriosis beginning 2 days after infection. Inflammatory responses in the brain were studied up to 30 days post-infection. Comparison of Lm-induced brain inflammation in normal C57BL/6 and miR-155-/- mice showed miR-155-/- mice had muted IFN-γ activation and M1 polarization of microglia, as well as reduced influxes of bone marrow-derived cells, particularly CD8+ T-lymphocytes, in the brain compared with non-mutated mice. To model blockade of miR-155 as a therapeutic adjunct to antibiotics, Lm-infected wildtype mice were injected with a miR-155 inhibitor starting with the first dose of antibiotics. These studies showed miR-155 inhibitor, but not the nucleic acid control, reduced numbers of CD8+ tissue-resident memory (TRM) T-lymphocytes present in the brains of infected mice, a finding that was confirmed in miR-155-/- animals. Current work is focused on developing an aged mouse model to study brain inflammation in response to bacterial infection, and identifying ways to ameliorate it, in this population of animals challenging to work with due to frailty and baseline alterations in brain inflammatory processes.

Information: Pieter Leenen p.leenen@erasmusmc.nl
Please register before Wednesday April 7 by e-mail to: secretariaat.immunologie@erasmusmc.nl
You will receive the link to the seminar after registration.

 

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