ROLE OF CHEMOKINE-CHEMOKINE RECEPTORS IN THE PATHOGENESIS OF SEVERE PLASMODIUM FALCIPARUM MALARIA IN CHILDREN: IMPLICATIONS FOR MALARIA-HIV INTERACTION

Molecular determinants of malaria pathogenesis are largely undefined. Chemokines and chemokine receptors, regulate immune responses, may thus determine malaria severity. Further, by regulating HIV pathogenesis, they may constitute a crucial link in malaria-HIV interaction. Understanding biologic mechanisms underlying malaria-HIV interaction has important public health utility in designing rational therapeutic and preventive strategies. Malaria could potentially modulate HIV-1 infection through alteration in expression of CD4 and chemokine receptors, required for cellular entry. This study has determined circulating levels and transcriptional profiles of β-chemokines (MIP-1α, MIP-1β, and RANTES) in ex vivo peripheral blood mononuclear cells (PBMCs) of children with varying degrees of malaria severity. Additional in vitro experiments assessed the effects of stimulation of PBMCs with crude hemozoin (Hz) or synthetic hemozoin (sHz) on CD4, β-chemokine and chemokine receptor (CCR5 and CXCR4) protein expression and transcript formation. Plasma MIP-1α and MIP-1β levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. β-chemokine gene expression closely matched circulating β-chemokine profile, illustrating that PBMCs are a primary source for β-chemokine production during malaria. Healthy children with a history of severe malaria had lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in RANTES production. In vitro experiments in PBMCs from healthy malaria-naïve donors showed that Hz and sHz promote a similar pattern of β-chemokine protein secretion and transcript expression. FACS analysis showed that Hz and sHz induced similar patterns of cellular surface expression of CD4, CCR5 and CXCR4 on PBMCs. Hz or sHz-exerted differential effects on CD14+ and CD3+ subsets, and this modulatory effect part to transcriptional regulation based on gene expression profiles obtained for respective antigens. Additional studies showed that HIV-1 replicates differently in monoctye-derived macrophages (MDMs) stimulated with either Hz or sHz. sHz enhanced HIV-1 replication while Hz had an inhibitory effect. Results presented here demonstrate a distinct profile of β-chemokine expression in children with severe malaria, which is promoted by P. falciparum derived hemozoin. Further, Hz modulates expression of surface antigens required for HIV-1 entry, defining a possible mechanism for HIV-malaria interaction

Selected Computing Research Papers Volume 7 June 2018

Contents Critical Evaluation of Arabic Sentimental Analysis and Their Accuracy on Microblogs (Maha Al-Sakran) Evaluating Current Research on Psychometric Factors Affecting Teachers in ICT Integration (Daniel Otieno Aoko) A Critical Analysis of Current Measures for Preventing Use of Fraudulent Resources in Cloud Computing (Grant Bulman) An Analytical Assessment of Modern Human Robot Interaction Systems (Dominic Button) Critical Evaluation of Current Power Management Methods Used in Mobile Devices (One Lekula) A Critical Evaluation of Current Face Recognition Systems Research Aimed at Improving Accuracy for Class Attendance (Gladys B. Mogotsi) Usability of E-commerce Website Based on Perceived Homepage Visual Aesthetics (Mercy Ochiel) An Overview Investigation of Reducing the Impact of DDOS Attacks on Cloud Computing within Organisations (Jabed Rahman) Critical Analysis of Online Verification Techniques in Internet Banking Transactions (Fredrick Tshane

Susceptibility patterns and the role of extracellular DNA in Staphylococcus epidermidis biofilm resistance to physico-chemical stress exposure

Abstract Background Over 65% of human infections are ascribed to bacterial biofilms that are often highly resistant to antibiotics and host immunity. Staphylococcus epidermidis is the predominant cause of recurrent nosocomial and biofilm-related infections. However, the susceptibility patterns of S. epidermidis biofilms to physico-chemical stress induced by commonly recommended disinfectants [(heat, sodium chloride (NaCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H2O2)] in domestic and human healthcare settings remains largely unknown. Further, the molecular mechanisms of bacterial biofilms resistance to the physico-chemical stresses remain unclear. Growing evidence demonstrates that extracellular DNA (eDNA) protects bacterial biofilms against antibiotics. However, the role of eDNA as a potential mechanism underlying S. epidermidis biofilms resistance to physico-chemical stress exposure is yet to be understood. Therefore, this study aimed to evaluate the susceptibility patterns of and eDNA release by S. epidermidis biofilm and planktonic cells to physico-chemical stress exposure. Results S. epidermidis biofilms exposed to physico-chemical stress conditions commonly recommended for disinfection [heat (60 °C), 1.72 M NaCl, solution containing 150 μL of waterguard (0.178 M NaOCl) in 1 L of water or 1.77 M H2O2] for 30 and 60 min exhibited lower log reductions of CFU/mL than the corresponding planktonic cells (p < 0.0001). The eDNA released by sub-lethal heat (50 °C)-treated S. epidermidis biofilm and planktonic cells was not statistically different (p = 0.8501). However, 50 °C-treated S. epidermidis biofilm cells released significantly increased eDNA than the untreated controls (p = 0.0098). The eDNA released by 0.8 M NaCl-treated S. epidermidis biofilm and planktonic cells was not significantly different (p = 0.9697). Conversely, 5 mM NaOCl-treated S. epidermidis biofilms exhibited significantly increased eDNA release than the corresponding planktonic cells (p = 0.0015). Further, the 50 μM H2O2-treated S. epidermidis biofilms released significantly more eDNA than the corresponding planktonic cells (p = 0.021). Conclusions S. epidermidis biofilms were less susceptible to physico-chemical stress induced by the four commonly recommended disinfectants than the analogous planktonic cells. Further, S. epidermidis biofilms enhanced eDNA release in response to the sub-lethal heat and oxidative stress exposure than the corresponding planktonic cells suggesting a role of eDNA in biofilms resistance to the physico-chemical stresses