Pathogen-associated molecular pattern (PAMP)
Several previous studies have suggested that the S protein of SARS-CoV-2
might function as a pathogen-associated molecular pattern (PAMP) to
drive neuroinflammatory responses through activation of TLRs, which are
widely expressed on macrophages and microglia and may function as
pattern recognition receptors (PRRs) to recognize molecular sequences
common to bacterial and viral pathogens. Microglia have been shown to
express a wide range of PRRs, including TLRs, NOD-like receptors, RAGE
and scavenger receptors. SARS-CoV-2 activates these receptors, possibly
eliciting neuroinflammatory responses and contributing to disease
progression and severity [19].
Astrocytes are also important components of the intrinsic immune
response in the CNS following viral infection. An increased plasma
concentration of glial fibrillary acidic protein (GFAP), a hallmark of
astrocyte activation, is commonly detected in patients with moderate and
severe COVID-19. As components of the BBB, astrocytes are highly
sensitive to peripheral inflammation. In addition to responding to
signals from microglia, astrocytes also rapidly respond to
proinflammatory cytokines secreted by endothelial cells. Astrocytes
express inflammatory molecules that contribute to neuroinflammation and
neurodegeneration upon exposure to activated proinflammatory microglia,
including proinflammatory cytokines such as IL-6, IL-1β and TNF-α;
PAMPs; and danger-associated molecular patterns. These data clearly
indicate that microglia and astrocytes participate in neuroinflammatory
responses to viral infection of the CNS [20].