Pentraxins in the activation and regulation of innate immunity

Daigo, Kenji; Inforzato, Antonio; Barajon, Isabella; Garlanda, Cecília; Bottazzi, Barbara; Meri, Seppo; Mantovani, Alberto

doi:10.1111/imr.12476

Cited by 94 publications

(75 citation statements)

References 183 publications

(381 reference statements)

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“…As a consequence, they can compete with FH for host surface binding and de‐regulate complement activity on certain surfaces such as apoptotic cells . Finally, members of the pentraxin family are known as context‐specific modulators of complement activity but seem to mediate their activity via binding to PRMs and regulators rather than by directly interacting with C3 fragments …”

Section: Complement C3: a Functional Hub In Innate Immunity And Beyondmentioning

confidence: 99%

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

349

295

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Summary As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target.

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Section: Complement C3: a Functional Hub In Innate Immunity And Beyondmentioning

confidence: 99%

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

349

295

View full text Add to dashboard Cite

show abstract

“…during inflammation) by various cell types, including vascular, stromal and innate immune cells [83]. While the short pentraxins CRP and SAP are composed primarily of a pentraxin domain, PTX3 has an additional ~160 residue domain at its N-terminal end [80, 84]. Both short and long pentraxins interact with components of the three complement pathways, including FH [74, 76] and C4BP [85, 86].…”

Section: Other Ligands Of Factor Hmentioning

confidence: 99%

Complement factor H in host defense and immune evasion

Parente

Clark

Inforzato

et al. 2016

Cell. Mol. Life Sci.

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162

147

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Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

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“…While CRP and SAP are mainly produced by liver upon IL‐6 induction, PTX3 is secreted by different cell types in response to different stimuli. TLR, inflammatory cytokines (such as IL‐1β and TNFα), microbial moieties (LPS or OmpA), and microorganisms induce the secretion of PTX3 by a variety of cell types, including dendritic cells (DCs), macrophages, fibroblasts, synovial cells, chondrocytes, adipocytes, mesangial cells, granulosa cells, and glial cells . PTX3 expression is stimulated in endothelial cells and vascular smooth muscle cells (SMCs) in response to modified low density lipoproteins (ox‐LDL) and anti‐inflammatory high‐density lipoproteins stimulation, while it is constitutive in lymphatic endothelial cells .…”

Section: Pentraxins: Ptx3mentioning

confidence: 99%

The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis

Erreni

Manfredi

Garlanda

et al. 2017

Immunological Reviews

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Tissue damage frequently occurs. The immune system senses it and enforces homeostatic responses that lead to regeneration and repair. The synthesis of acute phase molecules is emerging as a crucial event in this program. The prototypic long pentraxin PTX3 orchestrates the recruitment of leukocytes, stabilizes the provisional matrix in order to facilitate leukocyte and stem progenitor cells trafficking, promotes swift and safe clearance of dying cells and of autoantigens, limiting autoimmunity and protecting the vasculature. These non-redundant actions of PTX3 are necessary for the resolution of inflammation. Recent studies have highlighted the mechanisms by which PTX3 adapts the functions of innate immune cells, orchestrates tissue repair and contributes to select the appropriate acquired immune response in various tissues. Conversely, PTX3 continues to be produced in diseases where the inflammatory response does not resolve. It is therefore a valuable biomarker for more precise and personalized stratification of patients, often independently predicting clinical evolution and outcome. There is strong promise for novel therapies based on understanding the mechanisms with which PTX3 plays its homeostatic role, especially in regulating leukocyte migration and the resolution of inflammatory processes.

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Pentraxins in the activation and regulation of innate immunity

Cited by 94 publications

References 183 publications

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Complement factor H in host defense and immune evasion

The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis

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