Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation.

Components of the extracellular matrix (ECM), when exposed to body fluids may promote local complement activation and inflammation. Pathologic complement activation at the glomerular basement membrane and at the Bruch's membrane is implicated in renal and eye diseases, respectively. Binding of soluble complement inhibitors to the ECM, including factor H (FH), is important to prevent excessive complement activation.

Interaction of with extracellular matrix components resulting in immunomodulation and bacterial eradication.

is a major human pathogen that causes a variety of diseases ranging from mild skin and throat infections to fatal septicemia. In severe invasive infections, encounters and interacts with components of the extracellular matrix (ECM), including small leucine rich-proteoglycans (SLRPs). In this study, we report a novel antimicrobial role played by SLRPs biglycan, decorin, fibromodulin and osteoadherin, specifically in promoting the eradication of in a human sepsis model of infection.

Antibacterial Fusion Proteins Enhance Killing.

is a human-specific commensal of the respiratory tract and an opportunistic pathogen. It is one of the leading cause of otitis media in children and of acute exacerbations in patients with chronic obstructive pulmonary disease, resulting in significant morbidity and economic burden. Vaccines and new immunotherapeutic strategies to treat this emerging pathogen are needed.

C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections.

Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that Neisseria gonorrhoeae uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP).

The hijackers guide to escaping complement: Lessons learned from pathogens.

Pathogens that invade the human host are confronted by a multitude of defence mechanisms aimed at preventing colonization, dissemination and proliferation. The most frequent outcome of this interaction is microbial elimination, in which the complement system plays a major role. Complement, an essential feature of the innate immune machinery, rapidly identifies and marks pathogens for efficient removal.

The Molecular Basis of Human IgG-Mediated Enhancement of C4b-Binding Protein Recruitment to Group A Streptococcus.

infects over 700 million people worldwide annually. Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. We recently showed that human IgG increased C4BP binding to the bacterial surface, which promoted streptococcal immune evasion and increased mortality in mice.

Catch Me if You Can: Streptococcus pyogenes Complement Evasion Strategies.

The human host has evolved elaborate protection mechanisms to prevent infection from the billions of microorganisms to which it host is exposed and is home. One of these systems, complement, is an evolutionary ancient arm of innate immunity essential for combatting bacterial infection. Complement permits the efficient labelling of bacteria with opsonins, supports phagocytosis, and facilitates phagocyte recruitment to the site of infection through the production of chemoattractants.

Short Leucine-Rich Proteoglycans Modulate Complement Activity and Increase Killing of the Respiratory Pathogen .

The respiratory pathogen is a human-specific commensal that frequently causes acute otitis media in children and stimulates acute exacerbations in chronic obstructive pulmonary disease patients. The exact molecular mechanisms defining host-pathogen interactions promoting pathogenesis are not clearly understood. Limited knowledge hampers vaccine and immunotherapeutic development required to treat this emerging pathogen.

Assessment of Neutrophil Chemotaxis Upon G-CSF Treatment of Healthy Stem Cell Donors and in Allogeneic Transplant Recipients.

Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy.

Human IgG Increases Virulence of through Complement Evasion.

is an exclusively human pathogen that can provoke mild skin and throat infections but can also cause fatal septicemia. This gram-positive bacterium has developed several strategies to evade the human immune system, enabling to survive in the host. These strategies include recruiting several human plasma proteins, such as the complement inhibitor, C4b-binding protein (C4BP), and human (hu)-IgG through its Fc region to the bacterial surface to evade immune recognition.

Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen .

Bacteria can cause life-threatening infections, such as pneumonia, meningitis, or sepsis. Antibiotic therapy is a mainstay of treatment, although antimicrobial resistance has drastically increased over the years. Unfortunately, safe and effective vaccines against most pathogens have not yet been approved, and thus developing alternative treatments is important.

Correlating Bridging Ligand with Properties of Ligand-Templated [MnX] Clusters (X = Br, Cl, H, MeO).

Polynuclear manganese compounds have garnered interest as mimics and models of the water oxidizing complex (WOC) in photosystem II and as single molecule magnets. Molecular systems in which composition can be correlated to physical phenomena, such as magnetic exchange interactions, remain few primarily because of synthetic limitations. Here, we report the synthesis of a family of trimanganese(II) complexes of the type MnXL (X = Cl, H, and MeO) where L is a tris(β-diketiminate) cyclophane.

Dual transcriptome of the immediate neutrophil and Candida albicans interplay.

Background: Neutrophils are traditionally considered transcriptionally inactive. Compared to other immune cells, little is known about their transcriptional profile during interaction with pathogens.

Methods: We analyzed the meta-transcriptome of the neutrophil-Candida albicans interplay and the transcriptome of C.

PRELP Enhances Host Innate Immunity against the Respiratory Tract Pathogen .

Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity. We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue.

FACIN, a Double-Edged Sword of the Emerging Periodontal Pathogen Filifactor alocis: A Metabolic Enzyme Moonlighting as a Complement Inhibitor.

Periodontal disease is one of the most common inflammatory infectious diseases worldwide and it is associated with other syndromes, such as cardiovascular disease or rheumatoid arthritis. Recent advances in sequencing allowed for identification of novel periodontopathogens such as Gram-positive Filifactor alocis, but its virulence mechanisms remain largely unknown. We confirmed that F.

Insights into small molecule activation by multinuclear first-row transition metal cyclophanates.

The rational design of trimetallic transition metal clusters supported by a trinucleating cyclophane ligand, L(3-), and the reactivities of these complexes with dinitrogen and carbon dioxide are discussed. Emphasis is placed on the differences in the observed reactivity between these trimetallic cyclophane complexes and that of the mono- and dinuclear transition metal compounds.

Moonlighting of Helicobacter pylori catalase protects against complement-mediated killing by utilising the host molecule vitronectin.

Helicobacter pylori is an important human pathogen and a common cause of peptic ulcers and gastric cancer. Despite H. pylori provoking strong innate and adaptive immune responses, the bacterium is able to successfully establish long-term infections.

Moraxella catarrhalis Evades Host Innate Immunity via Targeting Cartilage Oligomeric Matrix Protein.

Moraxella catarrhalis is a respiratory tract pathogen commonly causing otitis media in children and acute exacerbations in patients suffering from chronic obstructive pulmonary disease. Cartilage oligomeric matrix protein (COMP) functions as a structural component in cartilage, as well as a regulator of complement activity. Importantly, COMP is detected in resident macrophages and monocytes, alveolar fluid, and the endothelium of blood vessels in lung tissue.

C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend.

C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500 kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75 kDa α-chains and often also one 40 kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains.

Reactivity of Hydride Bridges in High-Spin [3M-3(μ-H)] Clusters (M = FeII, CoII).

The designed [3M-3(μ-H)] clusters (M = Fe(II), Co(II)) Fe3H3L (1-H) and Co3H3L (2-H) [where L(3-) is a tris(β-diketiminate) cyclophane] were synthesized by treating the corresponding M3Br3L complexes with KBEt3H. From single-crystal X-ray analysis, the hydride ligands are sterically protected by the cyclophane ligand, and these complexes selectively react with CO2 over other unsaturated substrates (e.g.

Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors.

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition.

Nitride-bridged triiron complex and its relevance to dinitrogen activation.

Using a simple metathesis approach, the triiron(II) tribromide complex Fe3Br3L (1) reacts with tetrabutylammonium azide to afford the monoazide dibromide analogue Fe3(Br)2(N3)L (2) in high yield. The inclusion of azide was confirmed by IR spectroscopy with a ν(N3) = 2082 cm(-1) as well as combustion analysis and X-ray crystallography. Heating 2 in the solid state results in the complete loss of the azide vibration in the IR spectra and the isolation of the olive-green mononitride complex Fe3(Br)2(N)L (3).

An Air- and Water-Tolerant Zinc Hydride Cluster That Reacts Selectively With CO2.

The reaction of [Zn3Cl3L], in which L(3-) is a tris(β-diketiminate) cyclophane, with K(sBu)3BH afforded [Zn3(μ-H)3L] (2), as confirmed by NMR spectroscopy, NOESY, and X-ray crystallography. The complex 2 was air-stable and unreactive towards water, methanol, and other substrates (e.g.

Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.

Streptococcus pyogenes AP1, a strain of the highly virulent M1 serotype, uses exclusively protein H to bind the complement inhibitor C4b-binding protein (C4BP). We found a strong correlation between the ability of AP1 and its isogenic mutants lacking protein H to inhibit opsonization with complement C3b and binding of C4BP. C4BP bound to immobilized protein H or AP1 bacteria retained its cofactor activity for degradation of (125)I-C4b.