Complement system in diseases

Bacterial exo-α-sialidases subvert the complement system through desialylation

This study shows bacterial sialidases remove sialic acids from complement proteins, reducing complement activation and helping bacteria evade immune detection.

Temporal Dynamics of Complement Activation and Outcome in Patients with Acute Ischemic Stroke

The paper examines complement activation dynamics in acute ischemic stroke patients and controls, finding pathway-specific markers associated with outcomes.

Intracellular complement Factor B couples inflammatory sensing to metabolism, chromatin regulation and maladaptive tissue repair

The paper identifies an injury-induced complement program in kidney cells that couples inflammation to metabolism and chromatin regulation, promoting maladaptive fibrosis.

Kinetics of local C3 production orchestrates neutrophil recruitment in lung injury

This study shows lung-derived C3 initiates neutrophil recruitment in pneumonia before systemic C3, highlighting local complement's role in mucosal immunity.

Genetic architecture of immune-mediated thrombotic thrombocytopenic purpura in Han Chinese individuals

This study identifies two genetic loci associated with TTP in Han Chinese individuals, revealing structural variants in HLA-DRB1 that influence autoantigen presentation.

Antibody-mediated VWF targeting reconstitutes ADAMTS13 metalloproteinase activity and prevents thrombocytopenia in mice

This study develops ADAMTS13 mimetics that restore VWF cleavage and prevent thrombocytopenia in iTTP mice by using antibody-mediated substrate targeting.

Identification of a C3b-specific nanobody that does not bind C3 and blocks alternative pathway convertases

This study identifies a C3b-specific nanobody that binds C3b but not C3, and inhibits the alternative pathway convertases of the complement system.

Pre-clinical efficacy of a C4BP hexameric IgG Fc fusion protein against Neisseria gonorrhoeae

This paper demonstrates that a hexameric C4BP IgG Fc fusion protein significantly enhances complement-dependent bactericidal activity and reduces gonococcal vaginal colonization in mice.

Reducing sialylation in melanoma increases classical pathway-mediated complement activation

This study shows that reducing sialylation in melanoma enhances classical pathway-mediated complement activation, increasing C3 opsonization and membrane attack complex formation.

Percolation-inspired criticality in complement activation: universal scaling and transport-limited complement surface amplification

This study investigates complement activation on nanoparticle surfaces, showing it exhibits criticality with diverging order parameters and a transport-limited mechanism.

Unveiling the unique interaction mechanism of herpes simplex virus 2 glycoprotein C with C3b

This study determines the structure of herpes simplex virus 2 glycoprotein C interacting with C3b, revealing a unique mechanism to modulate the complement cascade.

Complement protein concentrations and activity in human cervical mucus

This study quantifies complement protein levels in cervical mucus across the menstrual cycle, finding significant variations in concentrations and functional activity compared to serum.

Internalized Components of Membrane Attack Complexes Disrupt Proteostasis and Acquire Alarmin-Like Properties

This study shows that C9, a component of membrane attack complexes, forms non-cytolytic intracellular aggregates that promote inflammation and EC activation through aggrephagy and NF-κB activation.

Platelet C5aR1 mediates sex-specific ischemia-driven revascularization through estradiol-dependent CXCL4 release

This study identifies a sex-specific mechanism where platelet C5aR1 mediates ischemia-driven revascularization through estradiol-dependent CXCL4 release, explaining sex differences in cardiovascular outcomes.

Development of a Complement Hemolysis Assay Using Aldehyde-Modified Human Erythrocytes

This paper develops a complement hemolysis assay using aldehyde-modified human erythrocytes, showing improved specificity and reliability compared to conventional methods.

Platelet C5aR1 Aggravates Myocardial Infarction through Platelet-Neutrophil Interactions and CXCL4-Dependent NET Release

This study shows that platelet C5aR1 worsens myocardial infarction by promoting neutrophil activation and NET release, and that targeting it can reduce cardiac damage.

An innate immune circuit involving the lectin pathway, complement and lung epithelial cells enforce barrier immunity to inhaled fungal disease

Monoclonal nephritic factors reveal insights into C3 convertase dynamics and dysregulation

The paper identifies monoclonal C3- and C5-nephritic factors, reveals their structural interactions with convertases, and explains their dual role in activating or inhibiting convertase activity.

C4BP occludes the non-opsonic interaction of Neisseria gonorrhoeae with human neutrophil CEACAMs

This study shows C4BP inhibits Neisseria gonorrhoeae's interaction with neutrophil CEACAMs, reducing phagocytic killing by blocking Opa-CEACAM binding.

Wrapping it Up: Structural Basis of ADAMTS13 Global Latency

This paper elucidates the structural basis of ADAMTS13 global latency by proposing a novel autoinhibition model where distal domains occlude substrate binding sites, explaining previously unexplained observations.

Excessive C5 conversion prevents C9 polymerisation and subsequent MAC-dependent killing of Klebsiella pneumoniae

This study shows that excessive C5 conversion in Klebsiella pneumoniae strains limits C9 polymerisation, preventing MAC-dependent killing, but adding C9 restores killing, indicating these strains are not truly resistant.

Glycan-coated nanoparticles mimicking the ischemic glycocalyx scavenge the complement system conferring protection after experimental ischemic stroke

The paper demonstrates that glycan-coated nanoparticles can sequester complement lectin pathway components, reducing ischemic brain injury in a mouse model.

Complement C3 recognition by C3 convertases

The paper presents cryo-EM structures of complement convertases and their complexes to elucidate the molecular mechanisms of C3 recognition and activation in the classical and alternative pathways.

Divergent roles for complement components C3 and C4 in controlling Klebsiella pneumoniae gut colonization and systemic dissemination

This study identifies distinct roles for complement proteins C3 and C4 in controlling Klebsiella pneumoniae gut colonization and systemic spread under different conditions.

The Contribution of the membrane-bound complement regulatory proteins CD46 and CD55 in phases of acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML)

This study investigates the differential expression of complement regulatory proteins CD46 and CD55 in acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) and finds their downregulation correlates with reduced cell viability upon silencing.

Mucosally sourced complement factor B modulates the host response to colitis

This study shows that locally produced complement factor B in the gut reduces colitis, highlighting its role in mucosal immunity.

Plasma Ficolins Enable Liver Macrophages to Capture Blood-Borne Bacteria by Recognizing Capsular Polysaccharides

This study shows plasma ficolins enable liver macrophages to capture blood-borne bacteria by recognizing capsular polysaccharides, enhancing immune response against encapsulated bacteria.

Structural insights into C3 convertase activity of the classical pathway of complement

The paper presents cryo-EM structures of classical pathway complement convertases and their substrate complex, revealing mechanisms of C3 cleavage and opsonin production.

Molecular basis of noncanonical complement C3 activation by histamine

This study identifies histamine as a novel activator of complement C3, forming C3h which accelerates complement activation and inflammation.

Bactericidal Membrane Attack Complex formation initiates at the new pole of E. coli

The paper tracks MAC pore localization on E. coli and finds that MAC deposition starts at the new bacterial pole, leading to inner membrane damage and halting division.