Cross-talk between the innate immune mechanisms, NETosis, complement activation and pattern recognition is integral to effective host defense and regulation of sterile inflammation. Dysregulated interactive balancing acts among the three mechanisms may lead to increased susceptibility to infections, autoimmune diseases and cancer. The antimicrobial death mechanism – NETosis (Neutrophil extracellular trap formation) is a key defensive armamentarium of neutrophils to trap invading pathogens. Using diverse pattern recognition receptors including TLRs, Fc receptors, and complement receptors, neutrophils sense the presence of pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) in an inflammatory milieu and release the extracellular traps. DAMPs induced sterile inflammation promotes excessive infiltration of neutrophils into the target tissue as well as potent activation of complement, leading to rapid generation of C3a and C5a. Interestingly, the first complement molecule of classical pathway, C1q, and Mannan binding lectin, the initiator of lectin complement pathway, also function as pattern recognition receptors. The integrant of neutrophils, majorly the antimicrobial peptides and extracellular DNA activates the components of the complement system which in turn augments the process resulting in inflammation, if not cleared. NETs release more DAMPs, thus, fueling a vicious cycle of amplified inflammation. In addition to the innate immune defense, the netting neutrophils also contribute to the pathogenesis of autoimmune diseases and cancer. The biomarkers of NETosis, particularly neutrophil elastase and MPO-DNA complex act as potential autoantigens in various autoinflammatory disorders like SLE, RA, diabetes, and psoriasis. NETs, DNA networks, are embedded with histones and elastase, that are potentially damaging the host. The pathophysiological role of complement-driven NET release in varied inflammatory disorders is poorly understood. Various cancers, including pancreatic cancer, have shown upregulated NETs. Hence, it is critical to decipher the functional entities and intensive interaction between NETosis, complement components and pattern recognition in regulating host immune responses.
The objective of this research topic compilation is to understand the basic mechanisms and factors involved in the interplay of these three prominent innate immune processes – NETosis, complement activation and pattern recognition in inflammatory mechanisms and their role in the pathophysiology and therapeutic advancements in inflammatory disorders. The research in this context essentially addresses to the new investigations carried out on the above direction and their translational implications, the goal is to explore a new avenue in the management of inflammatory disorders.
We, therefore welcome the innovative research work focusing on the basic and clinical aspects of systemic inflammatory disorders targeting the immune mechanisms mediated by neutrophils, complement components and pattern recognition receptors. Present and future aspects unravelling the complex triangular linkage of these innate processes and the development of drugs targeting the triad, holds promise to deliver newer therapeutic facets in modulating inflammation in chronic infections, autoimmune diseases and cancer.
This Research Topic will include the manuscripts unravelling the basic understanding and translational implications of pattern recognition receptors, complement components and their crosstalk. Importantly, this Research Topic is focused on research inferring an association of components of this triad with the pathophysiology of inflammatory disorders and scope of novel therapeutic strategies targeting these mechanisms. This research topic welcomes the submission of Original Research and Review/Mini-review manuscripts focusing on, but not strictly limited to the following sub-topics:
1. Molecular mechanisms of NETosis, complement activation, pattern recognition, their cross talks, modulation, and their role in inflammatory disorders.
2. Factors involved in NETosis, complement activation, pattern recognition receptor, their cross talks , and their implications for inflammatory disorders
3. Therapeutic opportunities of NETosis, complement activation, and pattern recognition for based novel drug candidate discovery.
4. Interaction of these three innate immune processes with adaptive immune responses and in disease development.
5. Advanced understanding on the individual and intersecting regulatory and signalling mechanisms of NETosis, complement activation, and pattern recognition.
6. Impairment of NETosis, complement activation, pattern recognition, and their immunological and pathological outcome.
7. Transcriptomics, proteomics and genomics to unravel novel markers of the innate immune pathways of NETosis, complement activation, and pattern recognition.
8. Significance of the factors involved in NETosis, complement components, pattern recognition and their interplay in cancer.
Cross-talk between the innate immune mechanisms, NETosis, complement activation and pattern recognition is integral to effective host defense and regulation of sterile inflammation. Dysregulated interactive balancing acts among the three mechanisms may lead to increased susceptibility to infections, autoimmune diseases and cancer. The antimicrobial death mechanism – NETosis (Neutrophil extracellular trap formation) is a key defensive armamentarium of neutrophils to trap invading pathogens. Using diverse pattern recognition receptors including TLRs, Fc receptors, and complement receptors, neutrophils sense the presence of pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) in an inflammatory milieu and release the extracellular traps. DAMPs induced sterile inflammation promotes excessive infiltration of neutrophils into the target tissue as well as potent activation of complement, leading to rapid generation of C3a and C5a. Interestingly, the first complement molecule of classical pathway, C1q, and Mannan binding lectin, the initiator of lectin complement pathway, also function as pattern recognition receptors. The integrant of neutrophils, majorly the antimicrobial peptides and extracellular DNA activates the components of the complement system which in turn augments the process resulting in inflammation, if not cleared. NETs release more DAMPs, thus, fueling a vicious cycle of amplified inflammation. In addition to the innate immune defense, the netting neutrophils also contribute to the pathogenesis of autoimmune diseases and cancer. The biomarkers of NETosis, particularly neutrophil elastase and MPO-DNA complex act as potential autoantigens in various autoinflammatory disorders like SLE, RA, diabetes, and psoriasis. NETs, DNA networks, are embedded with histones and elastase, that are potentially damaging the host. The pathophysiological role of complement-driven NET release in varied inflammatory disorders is poorly understood. Various cancers, including pancreatic cancer, have shown upregulated NETs. Hence, it is critical to decipher the functional entities and intensive interaction between NETosis, complement components and pattern recognition in regulating host immune responses.
The objective of this research topic compilation is to understand the basic mechanisms and factors involved in the interplay of these three prominent innate immune processes – NETosis, complement activation and pattern recognition in inflammatory mechanisms and their role in the pathophysiology and therapeutic advancements in inflammatory disorders. The research in this context essentially addresses to the new investigations carried out on the above direction and their translational implications, the goal is to explore a new avenue in the management of inflammatory disorders.
We, therefore welcome the innovative research work focusing on the basic and clinical aspects of systemic inflammatory disorders targeting the immune mechanisms mediated by neutrophils, complement components and pattern recognition receptors. Present and future aspects unravelling the complex triangular linkage of these innate processes and the development of drugs targeting the triad, holds promise to deliver newer therapeutic facets in modulating inflammation in chronic infections, autoimmune diseases and cancer.
This Research Topic will include the manuscripts unravelling the basic understanding and translational implications of pattern recognition receptors, complement components and their crosstalk. Importantly, this Research Topic is focused on research inferring an association of components of this triad with the pathophysiology of inflammatory disorders and scope of novel therapeutic strategies targeting these mechanisms. This research topic welcomes the submission of Original Research and Review/Mini-review manuscripts focusing on, but not strictly limited to the following sub-topics:
1. Molecular mechanisms of NETosis, complement activation, pattern recognition, their cross talks, modulation, and their role in inflammatory disorders.
2. Factors involved in NETosis, complement activation, pattern recognition receptor, their cross talks , and their implications for inflammatory disorders
3. Therapeutic opportunities of NETosis, complement activation, and pattern recognition for based novel drug candidate discovery.
4. Interaction of these three innate immune processes with adaptive immune responses and in disease development.
5. Advanced understanding on the individual and intersecting regulatory and signalling mechanisms of NETosis, complement activation, and pattern recognition.
6. Impairment of NETosis, complement activation, pattern recognition, and their immunological and pathological outcome.
7. Transcriptomics, proteomics and genomics to unravel novel markers of the innate immune pathways of NETosis, complement activation, and pattern recognition.
8. Significance of the factors involved in NETosis, complement components, pattern recognition and their interplay in cancer.
