Home About us Contact
|
Home About us Contact | ||
|
|
||
Confers Protection (confer + protection)
Selected AbstractsNovel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells,HEPATOLOGY, Issue 3 2010Avidan U. Neumann Antibodies are thought to exert antiviral activities by blocking viral entry into cells and/or accelerating viral clearance from circulation. In particular, antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) confer protection, by binding circulating virus. Here, we used mathematical modeling to gain information about viral dynamics during and after single or multiple infusions of a combination of two human monoclonal anti-HBs (HepeX-B) antibodies in patients with chronic hepatitis B. The antibody HBV-17 recognizes a conformational epitope, whereas antibody HBV-19 recognizes a linear epitope on the HBsAg. The kinetic profiles of the decline of serum HBV DNA and HBsAg revealed partial blocking of virion release from infected cells as a new antiviral mechanism, in addition to acceleration of HBV clearance from the circulation. We then replicated this approach in vitro, using cells secreting HBsAg, and compared the prediction of the mathematical modeling obtained from the in vivo kinetics. In vitro, HepeX-B treatment of HBsAg-producing cells showed cellular uptake of antibodies, resulting in intracellular accumulation of viral particles. Blocking of HBsAg secretion also continued after HepeX-B was removed from the cell culture supernatants. Conclusion: These results identify a novel antiviral mechanism of antibodies to HBsAg (anti-HBs) involving prolonged blocking of the HBV and HBsAg subviral particles release from infected cells. This may have implications in designing new therapies for patients with chronic HBV infection and may also be relevant in other viral infections. (HEPATOLOGY 2010;) [source] Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Benjamin D. Hedley Abstract Breast cancer metastasis suppressor 1 (BRMS1) inhibits the ability of multiple human and murine cancer cell lines to metastasize to lymph nodes, bones and lungs. Comparison of mRNA expression in metastatic MDA-MB-435 human carcinoma cells (435) and metastasis-suppressed BRMS1 transfectants (435/BRMS1) showed a marked (>90%) reduction of osteopontin (OPN) mRNA and protein expression in BRMS1-overexpressing cells. OPN expression is associated with disease progression in patients, with higher levels of OPN produced by cancer cells associated with poorer patient survival. Furthermore, OPN has been suggested to promote survival of cancer cells in response to stress, although the mechanisms by which this may occur remain poorly understood. This study tested the hypothesis that re-expression of OPN in metastasis-suppressed 435/BRMS1 cells would reverse metastasis suppression and confer protection from stress-induced apoptosis. A stable pooled population of OPN overexpressing 435/BRMS1 cells was created (435/BRMS1/OPN). OPN re-expression did not affect in vitro cell growth rates; however, increased anchorage independent growth/survival and protection from hypoxia-induced apoptosis was observed (p < 0.05). In vivo, OPN re-expression in BRMS1 transfected cells did not affect in vivo primary tumor growth but did increase the incidence of spontaneous metastasis to lymph nodes and lungs in mice. These novel findings suggest that OPN downregulation by BRMS1 may be responsible, at least in part, for BRMS1-mediated metastasis suppression by sensitizing cancer cells to stress induced apoptosis. These studies clarify one mechanism by which BRMS1 can suppress metastasis. © 2008 Wiley-Liss, Inc. [source] Monoclonal antibodies against a 62 kDa proteinase of Trichomonas vaginalis decrease parasite cytoadherence to epithelial cells and confer protection in micePARASITE IMMUNOLOGY, Issue 3 2004H. Hernández SUMMARY Trichomonas vaginalis infects the epithelium of the genital tract. The mechanism by which it invades the tissue leading to the disease is not thoroughly understood. However, results of several studies seem to agree that parasite adhesion to epithelium cells is the initial step leading to infection in women. T. vaginalis is associated with high levels of proteolytic activity. The role of some of these proteinases in the development of infection has been demonstrated. The current study establishes the role of a 62 kDa excretion,secretion proteinase in parasite cytoadherence. Monoclonal antibodies (MAbs) against this enzyme were tested for their ability to inhibit this process. Three stable hybrid producers of IgG1class MAbs (4D8, 1A8, 3C11) against the 62 kDa proteinase were obtained. Two of them (4D8 and 1A8) showed parasite recognition by immunofluorescence. Parasite cytoadherence to a monolayer of HeLa cells was inhibited by the 4D8, 1A8 and 3C11 antibodies. MAb 4D8 administered 24 h before a challenge with T. vaginalis by the intraperitoneal route was able to protect the majority of mice. Nitric oxide levels in the serum of animals inoculated with MAb 4D8 and challenged with the parasite were significantly different from those recorded in mice treated with an unrelated MAb. These studies show that an appropriate antibody against 62 kDa proteinase can help the host resist a challenge by the intraperitoneal route with T. vaginalis. [source] Mannan-binding lectin plasma levels in leprosy: deficiency confers protection against the lepromatous but not the tuberculoid formsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006L. N. Dornelles Summary Mannan-binding lectin (MBL) is an important component of the first-line defence against infections. Evidence has shown that MBL deficiency, reducing phagocytosis and internalization of intracellular pathogens may protect the host against intracellular infections such as leprosy. In this study, we speculated whether genetically determined low MBL serum levels confer protection against Mycobacterium leprae infection. One hundred and ninety-one patients with leprosy, presenting lepromatous (n = 118), tuberculoid (n = 31), dimorph (n = 30) and indeterminate (n = 12) clinical forms and 110 healthy controls matched with the patients according to sex, age and ethnic background were investigated. MBL concentrations were measured in a double-antibody enzyme immune assay and C-reactive protein (CRP) serum levels by nephelometry. A significant negative association of MBL low values (< 100 ng/ml) was observed with lepromatous patients when comparing with controls and tuberculoid patients [10/118, 8·47%versus 21/110, 19·09%P = 0·03 ,2 with Yates' correction, odds ratio (OR) 0·39, confidence interval (CI) 0·18,0·88 and 8/31, 25·81%, P = 0·02, OR 0·27, CI 0·09,0·75, respectively]. There was no significant difference in the distribution of MBL levels between patients and controls or among the clinical forms. The concentration of CRP was significantly increased in the patients (P = 0·0002) and in the lepromatous form (P = 0·0001) when compared to controls. A weak positive correlation between MBL and CRP levels was observed in the patients (P = 0·010, R = 0·255). These data suggest a protective role for MBL deficiency against the development of the most severe and multi-bacillary form of leprosy. [source] Anti-inflammatory properties of heat shock protein 70 and butyrate on Salmonella -induced interleukin-8 secretion in enterocyte-like Caco-2 cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005J. J. Malago Summary Intestinal epithelial cells secrete the chemokine interleukin (IL)-8 in the course of inflammation. Because heat shock proteins (Hsps) and butyrate confer protection to enterocytes, we investigated whether they modulate Salmonella enterica serovar Enteritidis (S. serovar Enteritidis)-induced secretion of IL-8 in enterocyte-like Caco-2 cells. Caco-2 cells incubated with or without butyrate (0,20 m M, 48 h) were infected with S. serovar Enteritidis after (1 h at 42°C, 6 h at 37°C) or without prior heat shock (37°C). Levels of Hsp70 production and IL-8 secretion were analysed using immunostaining of Western blots and enzyme-linked immunosorbent assay (ELISA), respectively. The cells secreted IL-8 in response to S. serovar Enteritidis and produced Hsp70 after heat shock or incubation with butyrate. The IL-8 secretion was inhibited by heat shock and butyrate concentrations as low as 0·2 m M for crypt-like and 1 m M for villous-like cells. In a dose-dependent manner, higher butyrate concentrations enhanced IL-8 secretion to maximal levels followed by a gradual but stable decline. This decline was associated with increasing production of Hsp70 and was more vivid in crypt-like cells. In addition, the higher concentrations abolished the heat shock inhibitory effect. Instead, they promoted the IL-8 production in heat-shocked cells even in the absence of S. serovar Enteritidis. We conclude that heat shock and low concentrations of butyrate inhibit IL-8 production by Caco-2 cells exposed to S. serovar Enteritidis. Higher butyrate concentrations stimulate the chemokine production and override the inhibitory effect of the heat shock. The IL-8 down-regulation could in part be mediated via production of Hsp70. [source] Nonsteroidal antiinflammatory drugs as therapeutic agents for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 3 2002Todd E. Golde One feature of the end-stage pathology of Alzheimer's disease (AD) is the presence of numerous inflammatory markers associated with the amyloid , protein (A,) deposits in the brain. Experimental data strongly suggests that A, aggregates can incite an inflammatory response, but there are also data suggesting that inflammation can promote A, production and deposition. Thus, antiinflammatory drugs may have some role in AD therapy. This idea is supported by epidemiologic data, which shows that long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) confers protection from the development of AD. Significantly, oral salicylates have not been consistently shown to confer protection. Such studies have raised questions regarding the target or targets of NSAIDs that account for their apparent protection from AD. We have recently found that some NSAIDs have a novel mechanism of action, namely, selective lowering of the pathogenic A,42 peptide, that could contribute to their efficacy in AD. Further study will be needed to determine if the classic antiinflammatory properties of NSAIDs, the A,42-lowering property, another known or unknown property, or a combination of these contributes to NSAIDs apparent ability to protect individuals from the development of AD. Drug Dev. Res. 56:415,420, 2002. © Wiley-Liss, Inc. [source] Haemophilus influenzae type b conjugate vaccinesIMMUNOLOGY, Issue 2 2004Dominic F. Kelly Summary Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein,polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons. [source] A controlled evaluation of monthly maintenance interpersonal psychotherapy in late-life depression with varying levels of cognitive functionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2008Kristen Carreira Abstract Objective To evaluate the effect of maintenance Interpersonal Psychotherapy (IPT) on recurrence rates and time to recurrence of major depression in elderly patients with varying levels of cognitive function. Methods/Design Two-year maintenance study of monthly maintenance IPT vs supportive clinical management (CM) in remitted depressed elderly who were participants in a previously reported placebo-controlled study of maintenance paroxetine and IPT (Reynolds et al., 2006). We used Cox regression analysis to test interactions between cognitive status (Dementia Rating Scale score) and treatment (IPT, CM) with respect to recurrence of major depression. Results We observed a significant interaction between cognitive status and treatment: lower cognitive performance was associated with longer time to recurrence in IPT than in CM (58 weeks vs 17 weeks) (HR,=,1.41 [95% CI,=,1.04, 1.91], p,=,0.03). Subjects with average cognitive performance showed no effect of maintenance IPT vs CM on time to recurrence (38 vs 32 weeks, respectively). Conclusion Monthly maintenance IPT confers protection against recurrence of major depression in elders with lower cognitive functioning. Copyright © 2008 John Wiley & Sons, Ltd. [source] JNK phosphorylates the HSF1 transcriptional activation domain: Role of JNK in the regulation of the heat shock responseJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2001Jeonghyeon Park Abstract The role of c-Jun NH2 -terminal kinase (JNK) signaling cascade in the stress-inducible phosphorylation of heat shock factor 1 (HSF1) was investigated using known agonists and antagonists of JNK. We showed that treatment of HeLa cells with MG132, a proteasome inhibitor and known JNK activator, caused the transcriptional activation domain of HSF1 to be targeted and phosphorylated by JNK2 in vivo. Dose-response and time course studies of the effects of heat shock and anisomycin treatment showed a close correlation of the activation of JNK and hyperphosphorylation of HSF1. SB203580 inhibited JNK at the 100 ,M concentration and significantly reduced the amount of hyperphosphorylated HSF1 upon heat shock or anisomycin treatment. SB203580 and dominant-negative JNK suppress hsp70 promoter-driven reporter gene expression selectively at 45°C but not at 42°C heat stress, suggesting that JNK would be preferentially associated with the protective heat shock response against severe heat stress. The possibility that JNK-mediated phosphorylation of HSF1 may selectively stabilize the HSF1 protein and confers protection to cells under conditions of severe stress is discussed. J. Cell. Biochem. 82: 326,338, 2001. © 2001 Wiley-Liss, Inc. [source] Pre-exposure to infectious hypodermal and haematopoietic necrosis virus or to inactivated white spot syndrome virus (WSSV) confers protection against WSSV in Penaeus vannamei (Boone) post-larvaeJOURNAL OF FISH DISEASES, Issue 10 2006J Melena Abstract Larvae and post-larvae of Penaeus vannamei (Boone) were submitted to primary challenge with infectious hypodermal and haematopoietic necrosis virus (IHHNV) or formalin-inactivated white spot syndrome virus (WSSV). Survival rate and viral load were evaluated after secondary per os challenge with WSSV at post-larval stage 45 (PL45). Only shrimp treated with inactivated WSSV at PL35 or with IHHNV infection at nauplius 5, zoea 1 and PL22 were alive (4.7% and 4%, respectively) at 10 days post-infection (p.i.). Moreover, at 9 days p.i. there was 100% mortality in all remaining treatments, while there was 94% mortality in shrimp treated with inactivated WSSV at PL35 and 95% mortality in shrimp previously treated with IHHNV at N5, Z1 and PL22. Based on viral genome copy quantification by real-time PCR, surviving shrimp previously challenged with IHHNV at PL22 contained the lowest load of WSSV (0,1 × 103 copies ,g,1 of DNA). In addition, surviving shrimp previously exposed to inactivated WSSV at PL35 also contained few WSSV (0,2 × 103 copies ,g,1 of DNA). Consequently, pre-exposure to either IHHNV or inactivated WSSV resulted in slower WSSV replication and delayed mortality. This evidence suggests a protective role of IHHNV as an interfering virus, while protection obtained by inactivated WSSV might result from non-specific antiviral immune response. [source] Activation of adenosine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: Therapeutic implications for Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2002Kwok-Keung Tai Abstract It is anticipated that further understanding of the protective mechanism induced by ischemic preconditioning will improve prognosis for patients of ischemic injury. It is not known whether preconditioning exerts beneficial actions in neurodegenerative diseases, in which ischemic injury plays a causative role. Here we show that transient activation of ATP-sensitive potassium channels, a trigger in ischemic preconditioning signaling, confers protection in PC12 cells and SH-SY5Y cells against neurotoxic effect of rotenone and MPTP, mitochondrial complex I inhibitors that have been implicated in the pathogenesis of Parkinson's disease. The degree of protection is in proportion to the bouts of exposure to an ATP-sensitive potassium channel opener, a feature reminiscent of ischemic tolerance in vivo. Protection is sensitive to a protein synthesis inhibitor, indicating the involvement of de novo protein synthesis in the protective processes. Pretreatment of PC12 cells with preconditioning stimuli FeSO4 or xanthine/xanthine oxidase also confers protection against rotenone-induced cell death. Our results demonstrate for the first time the protective role of ATP-sensitive potassium channels in a dopaminergic neuronal cell line against rotenone-induced neurotoxicity and conceptually support the view that ischemic preconditioning-derived therapeutic strategies may have potential and feasibility in therapy for Parkinson's disease. © 2002 Wiley-Liss, Inc. [source] Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-binding recombinant polypeptide confers protection against infection by respiratory and urogenital pathogensMOLECULAR MICROBIOLOGY, Issue 5 2005Darryl J. Hill Summary The human-specific pathogens Neisseria meningitidis, N. gonorrhoea, Haemophilus influenzae and Moraxella catarrhalis share the property of targeting the carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) expressed on human epithelia. CEACAMs are signalling receptors implicated in cell adhesion and regulation of several physiological functions. Their targeting by pathogens can lead to tissue invasion. Although the CEACAM-binding ligands of the bacteria are structurally diverse, they target a common site on the receptor. We have generated a recombinant polypeptide that blocks the interactions of the mucosal pathogens with human epithelial cells and antibodies against it inhibit M. catarrhalis interactions with the receptor. As such, it is a potential antimicrobial agent to prevent infection via a strategy unlikely to promote bacterial resistance and a vaccine candidate against M. catarrhalis. In addition, it could serve more widely as a novel research tool and as a potential therapeutic agent in CEACAM-based physiological disorders. [source] Oxalate exudation into the root-tip water free space confers protection from aluminum toxicity and allows aluminum accumulation in the symplast in buckwheat (Fagopyrum esculentum)NEW PHYTOLOGIST, Issue 2 2010Benjamin Klug Summary ,A better understanding of aluminum (Al) uptake and transport is expected to contribute to unravel the apparent contradiction between Al exclusion and Al accumulation in buckwheat. ,We studied the effect of Al supply on the root-tip Al and oxalate concentrations of the apoplastic water free space fluid (WFSF) and the symplast as affected by temperature, oxalate supply and the anion-channel blocker phenylglyoxal (PG). ,Aluminum supply rapidly activated the release of oxalate to the WFSF to establish a 1 : 1 Al to oxalate ratio. In the symplast, the Al concentration was 100 times higher than in the external solution, and the Al to oxalate ratio was 1 : 2. Loading and unloading of Al, but not of oxalate, into and from the symplast were reduced at low temperature and are thus under metabolic control. Application of PG reduced the constitutive and the Al-enhanced WFSF oxalate concentrations and enhanced Al-induced root-growth inhibition. Unlike a 1 : 3 Al to oxalate ratio, a 1 : 1 ratio ameliorated only partly Al-induced root-growth inhibition without affecting root-tip Al contents or WFSF Al concentrations. ,We present a hypothesis with an Al oxalate (Ox)+ plasma-membrane transporter in the root cortex and a xylem-loading Al citrate (Cit)n, transporter in the xylem parenchyma cells as key elements of Al accumulation in buckwheat. [source] Prophylaxis with Centella asiatica confers protection to prepubertal mice against 3-nitropropionic-acid-induced oxidative stress in brainPHYTOTHERAPY RESEARCH, Issue 6 2010George K. Shinomol Abstract While the usage of Centella asiatica (CA) is on the increase worldwide, evidence demonstrating its protective efficacy against neurotoxicants is scarce. Hence the present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of CA against 3-nitropropionic-acid(3-NPA)-induced oxidative stress in the brain of prepubertal mice. We assessed the degree of oxidative stress in cytoplasm of brain regions of male mice (4,wk- old) given CA prophylaxis (5,mg/kg bw) for 10 days followed by 3-NPA administration (i.p.75,mg/kg bw) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the brain of untreated mice as evident by enhanced malondialdehyde levels, reactive oxygen species (ROS) generation, hydroperoxides and protein carbonyls (a measure of protein oxidation) in striatum and other regions (cortex, cerebellum and hippocampus), while CA prophylaxis completely ameliorated the 3-NPA- induced oxidative stress. Depletion of glutathione (GSH) levels, total thiols, perturbations in antioxidant enzymes and cholinergic enzymes in brain discernible among 3-NPA-treated mice were predominantly restored to normalcy with CA prophylaxis. It is hypothesized that the prophylactic protection offered by CA extract against neurotoxicant exposure may be largely due to its ability to enhance GSH, thiols and antioxidant defenses in the brain of prepubertal mice. Copyright © 2009 John Wiley & Sons, Ltd. [source] Isolated CD39 Expression on CD4+ T Cells Denotes both Regulatory and Memory PopulationsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009Q. Zhou Foxp3+ regulatory T cells (Tregs) express both ectoenzymes CD39 and CD73, which in tandem hydrolyze pericellular ATP into adenosine, an immunoinhibitory molecule that contributes to Treg suppressive function. Using Foxp3GFP knockin mice, we noted that the mouse CD4+CD39+ T-cell pool contains two roughly equal size Foxp3+ and Foxp3, populations. While Foxp3+CD39+ cells are CD73bright and are the bone fide Tregs, Foxp3,CD39+ cells do not have suppressive activity and are CD44+CD62L,CD25,CD73dim/,, exhibiting memory cell phenotype. Functionally, CD39 expression on memory and Treg cells confers protection against ATP-induced apoptosis. Compared with Foxp3,CD39, naďve T cells, Foxp3,CD39+ cells freshly isolated from non-immunized mice express at rest significantly higher levels of mRNA for T-helper lineage-specific cytokines IFN-, (Th1), IL-4/IL-10 (Th2), IL-17A/F (Th17), as well as pro-inflammatory cytokines, and rapidly secrete these cytokines upon stimulation. Moreover, the presence of Foxp3,CD39+ cells inhibits TGF-, induction of Foxp3 in Foxp3,CD39, cells. Furthermore, when transferred in vivo, Foxp3,CD39+ cells rejected MHC-mismatched skin allografts in a much faster tempo than Foxp3,CD39, cells. Thus, besides Tregs, CD39 is also expressed on pre-existing memory T cells of Th1-, Th2- and Th17-types with heightened alloreactivity. [source] Surfactant protein D deficiency influences allergic immune responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2004B. Schaub Summary Background The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation. Objective The aim of this study is to characterize the immune responses of SP-D-deficient (SP-D,/,) mice in a kinetic model of allergic inflammation. We determined whether allergic parameters were enhanced in SP-D,/, mice in vivo. Further, we examined whether functional immune responses in vitro such as lymphocyte proliferation (LP) and cytokine production were modulated in the absence of SP-D. Methods In vivo, wild-type (WT) and SP-D,/, mice were sensitized and challenged with the allergen ovalbumin (OVA) and assessed for allergic parameters (bronchoalveolar lavage (BAL) eosinophils, IL-13 production, pulmonary IFN-,, IL-10 expression) at early time points (1 and 3 days of challenge) in comparison with late time points (7 days of challenge). In vitro, spleen cells from WT and SP-D,/, mice were stimulated with the mitogen concanavalin A (ConA) and lipid A (LpA) and analysed for LP, IL-13 and IFN-, production. Toll-like receptor 4 (TLR4), ligand for LpA, was assessed by mRNA expression and immunohistochemistry in vivo. Results Following allergen exposure in vivo, SP-D,/, mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-, expression at early time points compared with WT mice. IL-10 expression was increased at early time points in SP-D,/, compared with WT mice. Allergen-induced TLR4 expression was increased in WT, but not in SP-D,/, mice. After stimulation with LpA and ConA in vitro LP was increased and IFN-, concentration was decreased in SP-D,/, mice. Conclusion SP-D may be critical for the modulation of early stages of allergic inflammation in vivo. [source] Mannan-binding lectin plasma levels in leprosy: deficiency confers protection against the lepromatous but not the tuberculoid formsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006L. N. Dornelles Summary Mannan-binding lectin (MBL) is an important component of the first-line defence against infections. Evidence has shown that MBL deficiency, reducing phagocytosis and internalization of intracellular pathogens may protect the host against intracellular infections such as leprosy. In this study, we speculated whether genetically determined low MBL serum levels confer protection against Mycobacterium leprae infection. One hundred and ninety-one patients with leprosy, presenting lepromatous (n = 118), tuberculoid (n = 31), dimorph (n = 30) and indeterminate (n = 12) clinical forms and 110 healthy controls matched with the patients according to sex, age and ethnic background were investigated. MBL concentrations were measured in a double-antibody enzyme immune assay and C-reactive protein (CRP) serum levels by nephelometry. A significant negative association of MBL low values (< 100 ng/ml) was observed with lepromatous patients when comparing with controls and tuberculoid patients [10/118, 8·47%versus 21/110, 19·09%P = 0·03 ,2 with Yates' correction, odds ratio (OR) 0·39, confidence interval (CI) 0·18,0·88 and 8/31, 25·81%, P = 0·02, OR 0·27, CI 0·09,0·75, respectively]. There was no significant difference in the distribution of MBL levels between patients and controls or among the clinical forms. The concentration of CRP was significantly increased in the patients (P = 0·0002) and in the lepromatous form (P = 0·0001) when compared to controls. A weak positive correlation between MBL and CRP levels was observed in the patients (P = 0·010, R = 0·255). These data suggest a protective role for MBL deficiency against the development of the most severe and multi-bacillary form of leprosy. [source] | |||||||||||||||||||||||||