Infectious diseases 1081 Bacterial and viral infections

Bacterial and viral infections of brain parenchyma invariably trigger reactive astrogliosis and activation of microglia; these processes may be local (e.g. in the case of brain abscesses) or diffuse (e.g. upon encephalitis). Reactive astrogliosis and activation of microglia are components of the brain's defence reactions, and in fact their success very much determines the outcome of infection.

Glial reactions can be acute (e.g. in the case of acute meningitis or encephalitis) or chronic (e.g. upon infections evoked by Toxoplasma gondii, which persists in neurones). Sometimes, glial reactions can be the first step in pathogenesis of the disease, which often happens upon viral infections such as HIV (which is discussed in detail below) or Borna virus. In the latter case, reactive astrogliosis occurs prior to the onset of encephalitis, and astrocytes begin to produce many inflammatory proteins, including interferon-7-inducible protein and inflammatory protein-10, which are important for further development of the disease. It is quite possible that astrocytes become infected by Borna viruses early in the progression of the disease; and the virus-stimulated secretion of chemokines and cytokines as well as inflammatory proteins is important for attraction of invading T lymphocytes, able to cope with viral infection. In particular, astroglial synthesis and release of inflammatory protein-10 is a possible general mechanism of astroglial reaction to viruses, as similar changes were observed during CNS infections with hepatitis virus, adenovirus and lymphocytic choriomeningitis virus; inflammatory protein-10 also has a direct antiviral effect against herpes simplex virus.

Bacterial infections usually affect the subarachnoid space, and result in meningitis without affecting the brain parenchyma, and therefore, as a rule, glial reactions are relatively mild. Bacterial meningitis results in activation of numerous immuno-logical responses including activation of the complement system and release of C3a and C5a anaphylatoxins. The reactive glial cells are concentrated in brain layers located closely to the meninges, and may participate in local defensive and immune reactions. Certain bacterial infections, such as infections with grampositive Streptococcus pneumoniae may trigger over-activation of microglia (and indeed the pneumococcal cell walls are extremely efficient microglia activators), which may in turn be involved in diffuse brain damage; this particular role of activated microglia may be a reason for the exceptionally high mortality and treatment resistance of gram-positive brain infections.

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