Index: Karolinska Institutet: KI Solna: Department of Microbiology, Tumor and Cell Biology


The role of astrocytes and pericytes in bacterial invasion of the brain


Supervisor: Dr. Federico Iovino, Assistant Professor
Department: MTC
Postal Address: Bioclinicum, J7:20
Solnavägen 30, 17164 Solna Stockholm
Telephone: 0767504902

E-mail: federico.iovino@ki.se
Homepage: https://staff.ki.se/people/fediov


The bacterium Streptococcus pneumoniae (the pneumococcus) is the most frequently cause of bacterial meningitis, an infectious disease which occurs as consequence of a bacterial infection in the brain (1). Even though the mortality of bacterial meningitis is not extremely high varying from 10 to 30% depending on geographical region, this disease is still considered devastating from World Health Organization because 50% of meningitis survivors suffer from irreparable brain damages caused by the bacterial infection of the brain. Bacterial meningitis is usually treated with antibiotics, however bacteria can quickly adapt and develop new resistance. Therefore, we need new and different tools to fight bacterial infections. Pneumococci in the blood stream enter the brain by interacting with the blood-brain barrier (BBB), a specialized vascular system that separates the blood circulation from the brain. Our goal is to understand the molecular mechanism regulating bacterial invasion of the brain after passage across the BBB to develop new therapeutic strategies that interfere with such mechanisms to protect the brain from bacterial invasion.
Pecicytes are contractile cells surrounding the BBB and act as perivascular macrophages (2). Astrocytes are also in close contact with the BBB endothelium and provide the biochemical support for the BBB endothelial cells (3). During infections, astrocytes participate in immune responses releasing complement components and cytokines (4). It has not been investigated if pericytes and astrocytes, due to their physical contact with the BBB endothelium, facilitate the passage of pneumococci from the BBB to the brain. The aim of this project is to investigate the role of astrocytes and pericytes as “translocation bridges” for the bacteria to enter the brain.

References
1. Iovino et al (2016) Trends Microbiol. 24: 307-315.
2. Prager O et al (2017) Exp. Ther. Med. 13: 799–809.
3. Verkhratsky A and Butt A (2013) Front. Syst. Neurosci. 8: 17.
4. Sofroniew M and Vinters HV (2009) Acta Neuropathol. 119: 7–35.


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