C-reactive protein binds to short phosphoglycan repeats of secreted proteophosphoglycans and activates complement.

Human C-reactive protein (CRP) binds to lipophosphoglycan (LPG), a virulence factor of spp., through the repeating phosphodisaccharide region. We report here that both major components of promastigote secretory gel (PSG), the filamentous proteophosphoglycan (fPPG) and the secreted acid phosphatase (ScAP), are also ligands.

Characterization of Posttranslationally Modified Multidrug Efflux Pumps Reveals an Unexpected Link between Glycosylation and Antimicrobial Resistance.

The substantial rise in multidrug-resistant bacterial infections is a current global imperative. Cumulative efforts to characterize antimicrobial resistance in bacteria has demonstrated the spread of six families of multidrug efflux pumps, of which resistance-nodulation-cell division (RND) is the major mechanism of multidrug resistance in Gram-negative bacteria. RND is composed of a tripartite protein assembly and confers resistance to a range of unrelated compounds.

Mycobacterium tuberculosis infection is associated with increased B cell responses to unrelated pathogens.

Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.

Activity of Chitosan and Its Derivatives against Leishmania major and Leishmania mexicana .

There is an urgent need for safe, efficacious, affordable, and field-adapted drugs for the treatment of cutaneous leishmaniasis, which newly affects around 1.5 million people worldwide annually. Chitosan, a biodegradable cationic polysaccharide, has previously been reported to have antimicrobial, antileishmanial, and immunostimulatory activities.

Cytomegalovirus Antibody Responses Associated With Increased Risk of Tuberculosis Disease in Ugandan Adults.

Background: Recent evidence highlights human cytomegalovirus (HCMV) and immune activation as risk factors for tuberculosis disease. It is not known whether other herpesviruses are also implicated, nor whether a dose-response relationship exists between tuberculosis risk and herpes coinfection.

Methods: This nested case-control study used stored serum samples from 25 persons with tuberculosis up to 10 years before tuberculosis diagnosis and between 3 and 6 matched controls without tuberculosis from a rural Ugandan cohort.

Vitamin D (1,25(OH)D3) induces α-1-antitrypsin synthesis by CD4 T cells, which is required for 1,25(OH)D3-driven IL-10.

Studies to identify novel immune-regulatory functions of active vitamin D (1,25(OH)D3) in human CD4 T cells revealed that 1,25(OH)D3 potently induced expression of the gene SERPINA1, encoding the anti-protease α-1-antitrypsin. We confirmed α-1-antitrypsin protein expression by 1,25(OH)D3-treated CD4 T cells, but not in CD8 T cells or monocytes. α-1-Antitrypsin promotes anti-inflammatory IL-10 synthesis in other immune cell populations.

HIV, HCMV and mycobacterial antibody levels: a cross-sectional study in a rural Ugandan cohort.

Objectives: A growing evidence base implicates human cytomegalovirus (HCMV) as a risk factor for TB disease. We investigated total IgG and mycobacteria-specific antibodies in a cross-sectional study nested within a rural Ugandan General Population Cohort (GPC), in relation to HIV infection and the magnitude of HCMV IgG response.

Methods: Sera from 2189 individuals (including 27 sputum-positive TB cases) were analysed for antibodies against mycobacteria (Ag85A, PPD, LAM, ESAT6/CFP10) and HCMV, tetanus toxoid (TT) and total IgG.

Characterising antibody avidity in individuals of varied Mycobacterium tuberculosis infection status using surface plasmon resonance.

There is increasing evidence supporting a role for antibodies in protection against tuberculosis (TB), with functional antibodies being described in the latent state of TB infection. Antibody avidity is an important determinant of antibody-mediated protection. This study characterised the avidity of antibodies against Ag85A, an immunodominant Mycobacterium tuberculosis (M.

Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses.

QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses.

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized.

The comparative immunology of wild and laboratory mice, Mus musculus domesticus.

The laboratory mouse is the workhorse of immunology, used as a model of mammalian immune function, but how well immune responses of laboratory mice reflect those of free-living animals is unknown. Here we comprehensively characterize serological, cellular and functional immune parameters of wild mice and compare them with laboratory mice, finding that wild mouse cellular immune systems are, comparatively, in a highly activated (primed) state. Associations between immune parameters and infection suggest that high level pathogen exposure drives this activation.

IgG1 Fc N-glycan galactosylation as a biomarker for immune activation.

Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world.

The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode Product ES-62 Modulates Complement Activation.

Parasitic nematodes manufacture various carbohydrate-linked phosphorylcholine (PCh)-containing molecules, including ES-62, a protein with an N-linked glycan terminally substituted with PCh. The PCh component is biologically important because it is required for immunomodulatory effects. We showed that most ES-62 was bound to a single protein, C-reactive protein (CRP), in normal human serum, displaying a calcium-dependent, high-avidity interaction and ability to form large complexes.

Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK.

Background: BCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. In this study, the influence of geographical location, season of birth, timing of vaccination, micronutrient status (zinc) and inflammatory status (C-reactive protein, CRP) were assessed.

Methods: Immunogenicity was assessed by cytokine signature in culture supernatants from diluted whole blood samples stimulated with M.

C-reactive protein is essential for innate resistance to pneumococcal infection.

No deficiency of human C-reactive protein (CRP), or even structural polymorphism of the protein, has yet been reported so its physiological role is not known. Here we show for the first time that CRP-deficient mice are remarkably susceptible to Streptococcus pneumoniae infection and are protected by reconstitution with isolated pure human CRP, or by anti-pneumococcal antibodies. Autologous mouse CRP is evidently essential for innate resistance to pneumococcal infection before antibodies are produced.

Recombinant expression of goat milk serum amyloid A: preliminary studies of the protein and derived peptides on macrophage phagocytosis.

Serum Amyloid A3 (SAA3) protein is a member of a complex group of acute phase and constitutive proteins which have been related to several immune functions. Bovine milk SAA3 (M-SAA3) has been described to have a unique N-terminal TFLK motif responsible for up regulating mucin expression in the intestine lumen and therefore a protective gastrointestinal role. cDNA sequences encoding the protein goat M-SAA3 were successfully cloned from milk, mammary gland tissue and liver, expressed despite observed toxicity and purified as a soluble protein.

A Gel filled intravaginal transducer for extended measurements of intra-abdominal pressure.

Limitations of the standard urogynecological pressure transducers have not adequately provided reliable measurements of intra-abdominal pressure (IAP) during physical activities. A previous novel intravaginal pressure transducer (IVT) was developed in order to overcome the shortcomings in existing technology. The design of the IVT was validated though comparisons with existing pressure transducers in both the clinical and bench top settings.

The proinflammatory activity of recombinant serum amyloid A is not shared by the endogenous protein in the circulation.

Objective: Elevated serum levels of the acute-phase protein serum amyloid A (SAA) are a marker for active rheumatoid arthritis (RA), and SAA can also be found in the tissues of patients with active RA. Based on a number of studies with recombinant SAA (rSAA), the protein has been suggested to be a potent proinflammatory mediator that activates human neutrophils, but whether endogenous SAA shares these proinflammatory activities has not been directly addressed. The present study was undertaken to investigate whether SAA in the plasma of patients with RA possesses proinflammatory properties and activates neutrophils in a manner similar to that of the recombinant protein.

Early helminth infections are inversely related to anemia, malnutrition, and malaria and are not associated with inflammation in 6- to 23-month-old Zanzibari children.

Helminths aggravate anemia and malnutrition among school children. We studied this association in a cross-sectional study of 6- to 23-month-old Zanzibari children (N = 2322) and a sub-sample of 690 children matched on age and helminth infection status. Ascaris, hookworm, and Trichuris infections were diagnosed along with recent fever, malaria infection, mid-upper arm circumference (MUAC) and hemoglobin concentration (Hb).

Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections.

The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever.

Mechanistic investigation into complementary (antisense) peptide mini-receptor inhibitors of cytokine interleukin-1.

Sense peptides are coded for by the nucleotide sequence (read 5'-->3') of the sense (positive) strand of DNA. Conversely, a complementary peptide is coded for by the nucleotide sequence (read 5'-->3') of the complementary or antisense (negative) strand of DNA. In many instances, sense and corresponding complementary peptides have been observed to interact specifically.

The lipidation status of acute-phase protein serum amyloid A determines cholesterol mobilization via scavenger receptor class B, type I.

During the acute-phase reaction, SAA (serum amyloid A) replaces apoA-I (apolipoprotein A-I) as the major HDL (high-density lipoprotein)-associated apolipoprotein. A remarkable portion of SAA exists in a lipid-free/lipid-poor form and promotes ABCA1 (ATP-binding cassette transporter A1)-dependent cellular cholesterol efflux. In contrast with lipid-free apoA-I and apoE, lipid-free SAA was recently reported to mobilize SR-BI (scavenger receptor class B, type I)-dependent cellular cholesterol efflux [Van der Westhuyzen, Cai, de Beer and de Beer (2005) J.

Serum amyloid A is an innate immune opsonin for Gram-negative bacteria.

Serum amyloid A (SAA) is the major acute-phase protein in man and most mammals. Recently we demonstrated that SAA binds to many Gram-negative bacteria including Escherichia coli and Pseudomonas aeruginosa through outer membrane protein A (OmpA) family members. Therefore we investigated whether SAA altered the response of innate phagocytic cells to bacteria.

CD11b regulates recruitment of alveolar macrophages but not pulmonary dendritic cells after pneumococcal challenge.

Despite their close physical and functional relationships, alveolar macrophages (AMs) and pulmonary dendritic cells (pulDCs) have rarely been examined together in the context of infection. Using a nonlethal, resolving model of pneumonia caused by intranasal injection of Streptococcus pneumoniae, we demonstrate that AMs and pulDCs exhibit distinct characteristics during pulmonary inflammation. Recruitment of AMs and pulDCs occurred with different kinetics, and increased numbers of AMs resulted mainly from the appearance of a distinct subset of CD11b(High) AMs.