Meningococcal knee arthritis serogroup W-135. Case report

N. Meningitidis serogroup (A, B, C), are main causers of disease. Serogroup W-135 incidence is lower nowadays and, although it is increasing, is such an uncommon infection in adults. We report a case of a monoarthritis knee due to Neisseria meningitidis (W- 135) in an inmunocompetent 50 year-old male

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The contribution of both oxygen and nitrogen intermediates to the intracellular killing mechanisms of C1q-opsonized Listeria monocytogenes by the macrophage-like IC-21 cell line.

Listeria monocytogenes is a facultative intracellular pathogen which is internalized by host mammalian cells upon binding to their surface. Further listerial growth occurs in the cytosol after escape from the phagosomal-endosomal compartment. We have previously reported that C1q is able to potentiate L. monocytogenes phagocytosis upon bacterial opsonization by ingestion through C1q-binding structures. In this report, we analysed the post-phagocytic events upon internalization of C1q-opsonized L. monocytogenes and found an induction of macrophage (Mphi)-like IC-21 cell bactericidal mechanisms displayed by the production of oxygen and nitrogen metabolites. Both types of molecules are effective in L. monocytogenes killing. Further analysis of the cellular responses promoted by interaction of C1q with its surface binding structures, leads us to consider C1q as a collaborative molecule involved in Mphi activation. Upon interaction with surface binding structures, C1q was able to trigger and/or amplify the production of reactive oxygen and nitrogen intermediates induced by stimuli such as interferon-gamma and L. monocytogenes phagocytosis.

Oxidation of defined antigens allows protein unfolding and increases both proteolytic processing and exposes peptide epitopes which are recognized by specific T cells.

The participation of oxidative mechanisms in major histocompatibility complex (MHC) class II-restricted antigen presentation was studied in vitro. In general, antigen processing is inhibited when peritoneal macrophages (MO) are incubated with scavengers of reactive oxygen intermediates (ROI): mannitol (an.OH scavenger), dimethylurea (DMTU, which reacts with H2O2 and HOCl) and NCO-700 (an epoxysuccinic acid derivative which inhibits oxidant production by activated phagocytes and can scavenge reactive oxygen species in both NaOCl and hypoxanthine (XOD) systems). However, neither rotenone and antimycins (inhibitors of O-2 production at the NADH dehydrogenase and ubiquinone-cytochrome b regions, respectively) nor aminoguanidine (an inducible nitric oxide synthase inhibitor) impaired antigen presentation, thus indirectly discarding the participation of mitochondrial oxidation and reactive nitrogen intermediates (RNI) in antigen processing. ROI scavengers do not inhibit the MHC class II-restricted presentation of antigens that need processing but have their disulphide bonds reduced. It can be shown that oxidation of protein antigens (either by chlorination or performic acid treatment) allow protein unfolding and enhance both processing and exposure of immunogenic epitopes to specific T cells.

Host cell heparan sulfate proteoglycans mediate attachment and entry of Listeria monocytogenes, and the listerial surface protein ActA is involved in heparan sulfate receptor recognition.

The mechanisms by which the intracellular pathogen Listeria monocytogenes interacts with the host cell surface remain largely unknown. In this study, we investigated the role of heparan sulfate proteoglycans (HSPG) in listerial infection. Pretreatment of bacteria with heparin or heparan sulfate (HS), but not with other glycosaminoglycans, inhibited attachment and subsequent uptake by IC-21 murine macrophages and CHO epithelial-like cells. Specific removal of HS from target cells with heparinase III significantly impaired listerial adhesion and invasion. Mutant CHO cells deficient in HS synthesis bound and internalized significantly fewer bacteria than wild-type cells did. Pretreatment of target cells with the HS-binding proteins fibronectin and platelet factor 4, or with heparinase III, impaired listerial infectivity only in those cells expressing HS. Moreover, a synthetic peptide corresponding to the HS-binding ligand in Plasmodium falciparum circumsporozoite protein (pepPf1) inhibited listerial attachment to IC-21 and CHO cells. A motif very similar to the HS-binding site of pepPf1 was found in the N-terminal region of ActA, the L. monocytogenes surface protein responsible for actin-based bacterial motility and cell-to-cell spread. In the same region of ActA, several clusters of positively charged amino acids which could function as HS-binding domains were identified. An ActA-deficient mutant was significantly impaired in attachment and entry due to altered HS recognition functions. This work shows that specific interaction with an HSPG receptor present on the surface of both professional and nonprofessional phagocytes is involved in L. monocytogenes cytoadhesion and invasion and strongly suggests that the bacterial surface protein ActA may be a ligand mediating HSPG receptor recognition.

Iron salts and iron-containing porphyrins block presentation of protein antigens by macrophages to MHC class II-restricted T cells.

In this report we present evidence indicating that red blood cells (RBC) and a soluble lysate derived from them, but neither RBC membranes nor several highly purified erythrocytic glycolipids, impaired antigen presentation. Hematoporphyrin and some defined hemoglobin degradation products (specifically iron-containing porphyrins) are the molecules responsible for antigen presentation inhibition in M phi. Although these metalloporphyrins did not inhibit antigen presentation in B cells or dendritic cells (DC), iron salts impaired antigen presentation in all antigen presenting cells (APC) tested. These effects were time and dose-dependent and occurred at the level of intracellular antigen processing, mainly because: (i) The inhibition was nontoxic; (ii) it was reversible with time; (iii) neither antigen uptake and catabolism nor de novo synthesis of IA molecules were affected; and (iv) it did not inhibit peptide binding to IA molecules and recognition by T cells. Finally, iron salts and metalloporphyrins generated lipid peroxidation by-products in APC in a dose-dependent manner. Production of lipid peroxides was clearly correlated with antigen processing interference. It is suggested that some porphyrins and free iron could be responsible for peroxidation of key lipids involved in specific protein interactions in antigen processing. These results may help to explain, at least partly, the impaired cellular immunity observed in several disorders associated with enhanced erythrophagocytosis and/or iron overload.