Innate immunity and neuroinflammation

Abstract

Inflammation of central nervous system (CNS) is usually associated with trauma and infection. Neuroinflammation occurs in close relation to trauma, infection, and neurodegenerative diseases. Low-level neuroinflammation is considered to have beneficial effects whereas chronic neuroinflammation can be harmful. Innate immune system consisting of pattern-recognition receptors, macrophages, and complement system plays a key role in CNS homeostasis following injury and infection. Here, we discuss how innate immune components can also contribute to neuroinflammation and neurodegeneration.

Figure 1

Schematic diagram showing structure of TLR and NLR family. TLR: toll-like receptor; NLRP: NOD-like receptor containing pyrin domain; NLRC: NOD-like receptor containing NLR-containing caspase activation and recruitment domain; NLRB: NOD-like receptor containing baculovirus inhibitor of apoptosis protein repeat domain; LRR: leucine-rich repeat; TIR: toll/il-1 receptor; PYD: pyrin domain; CARD: caspase activation and recruitment domain; BIR: baculovirus inhibitor of apoptosis protein repeat.   The figure shows the structure of a TLR containing a TIR domain present inside nucleus which is involved in signalling pathway and an LRR domain present in the cytoplasm which is involved in pathogen recognition. NLR are intracellular receptors containing a C-terminal LRR domain, a central NACHT domain, and a variable N-terminal domain which can be a PYD, a CARD, or a BIR domain.

Figure 2

The complement system. Complement regulators are indicated in red. MBL: mannan-binding lectin; MASP: MBL-associated serine protease; C4BP: C4b-binding protein; CR1: complement receptor 1. The complement system consists of 3 initiating pathways: classical pathway, lectin pathway, and alternative pathway. The classical pathway is usually activated by antigen-antibody complexes, the lectin pathway is activated by microbes with MBL-MASP complex, and the alternative pathway is activated spontaneously by hydrolysis of C3 to C3(H₂O). All 3 pathways lead to formation of C3 convertase, followed by C5 convertase, ultimately leading to formation of membrane attack complex. In this process, anaphylatoxins C3a and C5a are also released. The complement system is kept in check by a number of regulators.