Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies reactive with phosphorylcholine (PC) are ubiquitous in human sera, but the antigens stimulating their production and their function are not clear. Previous studies have shown that a significant proportion of dental plaque bacteria contain PC as determined by reactivity with PC-specific mouse myeloma proteins and monoclonal antibodies. Additionally, serum antibody concentrations of immunoglobulin (IgG) G anti-PC are higher in sera of individuals who have experienced periodontal attachment loss than those who are periodontally healthy. These data implicate the oral microflora as a source of antigen-stimulating anti-PC responses. Recent data also indicate that antibodies with specificity for PC are elevated in ApoE-deficient mice, a model for studies of athersclerosis, and that such antibodies bound oxidized low-density lipoproteins (LDL) (oxLDL) in atherosclerotic plaques. These data prompted the hypothesis that human anti-PC could bind to both oral bacteria and human oxLDL, and that these antigens are cross-reactive. We therefore examined the ability of human anti-PC to bind to PC-bearing strains of oral bacteria using enzyme-linked immunosorbent inhibition assays and by assessment of direct binding of affinity-purified human anti-PC to PC-bearing Actinobacillus actinomycetemcomitans. Our results indicated that PC-bearing strains of Streptococcus oralis, Streptococcus sanguis, Haemophilus aphrophilus, Actinomyces naeslundii, Fusobacterium nucleatum, and A. actinomycetemcomitans, as well as a strain of Streptococcus pneumoniae, absorbed up to 80% of anti-PC IgG antibody from human sera. Furthermore, purified anti-PC bound to a PC-bearing strain of A. actinomycetemcomitans but only poorly to a PC-negative strain. OxLDL also absorbed anti-PC from human sera, and oxLDL but not LDL reacted with up to 80% of the anti-PC in human sera. Furthermore, purified anti-PC bound directly to oxLDL but not to LDL. The data indicate that PC-containing antigens on a variety of common oral bacteria are cross-reactive with neoantigens expressed in oxLDL. We propose that PC-bearing dental plaque microorganisms may induce an antibody response to PC that could influence the inflammatory response associated with atherosclerosis.
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PMID:Phosphorylcholine-dependent cross-reactivity between dental plaque bacteria and oxidized low-density lipoproteins. 1159 29

Infection of the aorta usually results from septic embolization to the vasa vasorum, hematogenous seeding of an existing aneurysm, or extension from a contiguous site of infection. The diagnosis should be considered in patients, often men over the age of 50 years with atherosclerosis, who present with fever, abdominal pain, palpable abdominal mass, and leukocytosis, with or without positive blood cultures. In the pre-antibiotic area, infectious aortitis was largely a complication of infective endocarditis, and was usually caused by group A streptococci, Streptococcus pneumoniae, or Haemophilus influenzae. Now a diverse array of bacteria and fungi has been associated, most commonly Salmonella species, which comprise nearly one third of the abdominal aortic infections and Staphylococcus aureus. Computed tomography is the most useful imaging modality. Medical treatment alone carries a high mortality, whereas the mortality with surgery combined with antimicrobial treatment is lower. Empiric antibiotics effective against S. aureus and gram-negative rods, such as Salmonella, should be initiated in cases identified before microbiologic diagnosis. Surgical debridement and revascularization should be completed early because delay may lead to aneurysm rupture, which increases mortality. The intent of surgery is to 1) control hemorrhage, if the aneurysm has ruptured; 2) confirm the diagnosis; 3) control sepsis; and 4) reconstruct the arterial vasculature. The patient should remain on parenteral or oral antibiotics for at least 6 weeks, perhaps longer, to assure full eradication of the pathogen and prevent recurrent infection. Close medical follow-up is indicated and includes serial blood cultures and computed tomography scans.
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PMID:Infectious Aortitis. 1593 17

B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2-/-) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2-/- mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae, but not PC-negative nontypeable Haemophilus influenzae, relative to wild-type mice. PD-L2-/- mice had significantly increased PC-specific CD138+ splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 Id. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated that B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naive PD-L2-/- mice and irradiated chimeras reconstituted with PD-L2-/- B cells had significantly higher levels of IL-5, a potent stimulator of B-1 cell Ab production. PD-L2 mAb blockade of wild-type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PD-L2 mAb blockade significantly increased IL-5+ T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PD-L2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis.
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PMID:PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5-Dependent Mechanism. 2876 24