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Pattern recognition receptors (PRRs) and inflammasomes are a key part of the anti-viral innate immune system as they detect conserved viral pathogen-associated molecular patterns (PAMPs). A successful host response to viral infections critically depend on the initial activation of PRRs by viruses, mainly by viral DNA and RNA. The signalling pathways activated by PRRs leads to the expression of pro-inflammatory cytokines, to recruit immune cells, and type I and type III interferons which leads to the induction of interferon stimulated genes (ISG), powerful virus restriction factors that establish the "antiviral state". Inflammasomes contribute to anti-viral responses through the maturation of interleukin (IL)-1 and IL-18 and through triggering pyroptotic cell death. The activity of the innate immune system along with the adaptive immune response normally leads to successful virus elimination, although disproportionate innate responses contribute to viral pathology. In this review we will discuss recent insights into the influence of PRR activation and inflammasomes on viral infections and what this means for the mammalian host. We will also comment on how specific PRRs and inflammasomes may be relevant to how SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, interacts with host innate immunity.

SARM is the fifth and most conserved member of the Toll/Il-1 Receptor (TIR) adaptor family. However, unlike the other TIR adaptors, MyD88, Mal, TRIF and TRAM, SARM does not participate in transducing signals downstream of TLRs. By contrast SARM inhibits TLR signalling by interacting with the adaptors TRIF and MyD88. In addition, SARM also has positive roles in innate immunity by activating specific transcriptional programs following immune challenge. SARM has a pivotal role in activating different forms of cell death following cellular stress and viral infection. Many of these functions of mammalian SARM are also reflected in SARM orthologues in lower organisms such as C. elegans and Drosophila. SARM expression is particularly enriched in neurons of the CNS and SARM has a critical role in neuronal death and in axon degeneration. Recent fascinating molecular insights have been revealed as to the molecular mechanism of SARM mediated axon degeneration. SARM has been shown to deplete NAD+ by possessing intrinsic NADase activity in the TIR domain of the protein. This activity can be activated experimentally by forced dimerization of the TIR domain. It is thought that this activity of SARM is normally switched off by the axo-protective activities of NMNAT2 which maintain low levels of the NAD+ precursor NMN. Therefore, there is now great excitement in the field of SARM research as targeting this enzymatic activity of SARM may lead to the development of new therapies for neurodegenerative diseases such as multiple sclerosis and motor neuron disease.

A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses and are also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.