Blood-brain crosstalk: the roles of neutrophils, platelets, and neutrophil extracellular traps in neuropathologies.

Systemic inflammation, neurovascular dysfunction, and coagulopathy often occur concurrently in neuropathologies. Neutrophils and platelets have crucial synergistic roles in thromboinflammation and are increasingly suspected as effector cells contributing to the pathogenesis of neuroinflammatory diseases. In this review, we summarize the roles of platelet-neutrophil interactions in triggering complex pathophysiological events affecting the brain that may lead to the disruption of brain barriers, infiltration of toxic factors into the parenchyma, and amplification of neuroinflammation through the formation of neutrophil extracellular traps (NETs). We highlight the clinical significance of thromboinflammation in neurological disorders and examine the contributions of damage-associated molecular patterns (DAMPs) derived from platelets and neutrophils. These DAMPs originate from both infectious and non-infectious risk factors and contribute to the activation of inflammasomes during brain disorders. Finally, we identify knowledge gaps in the molecular mechanisms underlying neurodegenerative disease pathogenesis and emphasize the potential of interventions targeting platelets and neutrophils to treat neuroinflammatory diseases.

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections.

Cell death is an essential immunological apparatus of host defense, but dysregulation of mutually inclusive cell deaths poses severe threats during microbial and parasitic infections leading to deleterious consequences in the pathological progression of infectious diseases. Nucleotide-binding oligomerization domain (NOD)-Leucine-rich repeats (LRR)-containing receptors (NLRs), also called nucleotide-binding oligomerization (NOD)-like receptors (NLRs), are major cytosolic pattern recognition receptors (PRRs), their involvement in the orchestration of innate immunity and host defense against bacteria, viruses, fungi and parasites, often results in the cleavage of gasdermin and the release of IL-1ß and IL-18, should be tightly regulated. NLRs are functionally diverse and tissue-specific PRRs expressed by both immune and non-immune cells. Beyond the inflammasome activation, NLRs are also involved in NF-κB and MAPK activation signaling, the regulation of type I IFN (IFN-I) production and the inflammatory cell death during microbial infections. Recent advancements of NLRs biology revealed its possible interplay with pyroptotic cell death and inflammatory mediators, such as caspase 1, caspase 11, IFN-I and GSDMD. This review provides the most updated information that caspase 8 skews the NLRP3 inflammasome activation in PANoptosis during pathogen infection. We also update multidimensional roles of NLRP12 in regulating innate immunity in a content-dependent manner: novel interference of NLRP12 on TLRs and NOD derived-signaling cascade, and the recently unveiled regulatory property of NLRP12 in production of type I IFN. Future prospects of exploring NLRs in controlling cell death during parasitic and microbial infection were highlighted.