The relationship of Plasmodium falciparum humeral immunity with HIV-1 immunosuppression and treatment efficacy in Zambia

<p>Abstract</p> <p>Background</p> <p>HIV-1 infection affects malaria humeral immunity during pregnancy, but data for non-pregnant adults are lacking. This study reports the impact of HIV-1 infection and other variables on the level of malaria humeral immunity in adults with clinical malaria and whether humeral immune suppression was a risk factor for treatment failure.</p> <p>Methods</p> <p>Sera of 224 HIV-1 infected and 115 uninfected adults were compared for IgG to merozoite antigens AMA-1 and MSP2 (3D7 and FC27 types) determined by ELISA, and for IgG to the Variant Surface Antigens (VSA) of three different parasite line E8B, A4 and HCD6 determined by flow cytometry.</p> <p>Results</p> <p>Compared to HIV-1 uninfected adults, AMA-1 IgG was lower in HIV-1 infected (<it>P </it>= 0.02) and associated with low CD4 count AMA-1 IgG (<it>P </it>= 0.003). Low IgG to all three merozoite antigens was associated with less anemia (<it>P </it>= 0.03). High parasite load was associated with low MSP2 IgG 3D7 and FC27 types (<it>P </it>= 0.02 and <it>P </it>= 0.08). Antibody levels to VSA did not differ between HIV-1 infected and uninfected adults. However, low VSA IgGs were associated with high parasite load (<it>P </it>≤ 0.002 for each parasite line) and with treatment failure (<it>P </it>≤ 0.04 for each parasite line).</p> <p>Conclusion</p> <p>HIV-1 affects humeral responses to AMA-1, but seems to marginally or not affect humeral responses to other merozoite antigens and VSAs. The latter were important for controlling parasite density and predict treatment outcome.</p

Complete genome sequence of the Clostridium difficile laboratory strain 630Δerm reveals differences from strain 630, including translocation of the mobile element CTn5

Molecular Technology and Informatics for Personalised Medicine and Healt

Identification of the Unwinding Region in the Clostridioides difficile Chromosomal Origin of Replication

Faithful DNA replication is crucial for viability of cells across all kingdoms. Targeting DNA replication is a viable strategy for inhibition of bacterial pathogens. Clostridioides difficile is an important enteropathogen that causes potentially fatal intestinal inflammation. Knowledge about DNA replication in this organism is limited and no data is available on the very first steps of DNA replication. Here, we use a combination of in silico predictions and in vitro experiments to demonstrate that C. difficile employs a bipartite origin of replication that shows DnaA-dependent melting at oriC2, located in the dnaA-dnaN intergenic region. Analysis of putative origins of replication in different clostridia suggests that the main features of the origin architecture are conserved. This study is the first to characterize aspects of the origin region of C. difficile and contributes to our understanding of the initiation of DNA replication in clostridia

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Involvement of Surfactant Protein D in Ebola Virus Infection Enhancement via Glycoprotein Interaction

International audienceSince the largest 2014⁻2016 Ebola virus disease outbreak in West Africa, understanding of Ebola virus infection has improved, notably the involvement of innate immune mediators. Amongst them, collectins are important players in the antiviral innate immune defense. A screening of Ebola glycoprotein (GP)-collectins interactions revealed the specific interaction of human surfactant protein D (hSP-D), a lectin expressed in lung and liver, two compartments where Ebola was found in vivo. Further analyses have demonstrated an involvement of hSP-D in the enhancement of virus infection in several in vitro models. Similar effects were observed for porcine SP-D (pSP-D). In addition, both hSP-D and pSP-D interacted with Reston virus (RESTV) GP and enhanced pseudoviral infection in pulmonary cells. Thus, our study reveals a novel partner of Ebola GP that may participate to enhance viral spread

Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung and salivary gp-340 are identical in protein sequence, salivary gp-340 from one donor had significantly greater antiviral activity against avian-like IAV strains which preferentially bind sialic acids in α(2,3) linkage. A greater density of α(2,3)-linked sialic acids was present on the salivary gp-340 from this donor as compared with salivary gp-340 from another donor or several preparations of lung gp-340. Hence, the specificity of sialic acid linkages on gp-340 is an important determinant of anti-IAV activity. Gp-340 binds to SP-D (surfactant protein D), and we previously showed that lung gp-340 has co-operative interactions with SP-D in viral neutralization and aggregation assays. We now report that salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of SP-D. This effect was associated with greater binding of salivary gp-340 to the carbohydrate recognition domain of SP-D as compared with the binding of lung gp-340. These findings may relate to inter-individual variations in innate defence against highly pathogenic IAV and to effects of aspiration of oral contents on SP-D-mediated lung functions