Biology subjects

Glans, H.

Publications and source records attributed to Glans, H..

3 recordsLinked to original sources

bioRxiv2021

High genome plasticity and frequent genetic exchange in Leishmania tropica isolates from Afghanistan, Iran and Syria

BackgroundThe kinetoplastid protozoan Leishmania tropica mainly causes cutaneous leishmaniasis in humans in the Middle East, and relapse or treatment failure after treatment are common in this area. L. tropicas digenic life cycle includes distinct stages in the vector sandfly and the mammalian host. Sexual reproduction and genetic exchange appear to occur more frequently than in other Leishmania species. Understanding these processes is complicated by chromosome instability during cell division that yields aneuploidy, recombination and heterozygosity. This combination of rare recombination and aneuploid permits may reveal signs of hypothetical parasexual mating, where diploid cells fuse to form a transient tetraploid that undergoes chromosomal recombination and gradual chromosomal loss. Methodology/Principal FindingsThe genome-wide SNP diversity from 22 L. tropica isolates showed chromosome-specific runs of patchy heterozygosity and extensive chromosome copy number variation. All these isolates were collected during 2007-2017 in Sweden from patients infected in the Middle East and included isolates from a patient possessing two genetically distinct leishmaniasis infections three years apart with no evidence of re-infection. We found differing ancestries on the same chromosome (chr36) across multiple samples: matching the reference genome with few derived alleles, followed by blocks of heterozygous SNPs, and then by clusters of homozygous SNPs with specific recombination breakpoints at an inferred origin of replication. Other chromosomes had similar marked changes in heterozygosity at strand-switch regions separating polycistronic transcriptional units. Conclusion/SignificanceThese large-scale intra- and inter-chromosomal changes in diversity driven by recombination and aneuploidy suggest multiple mechanisms of cell reproduction and diversification in L. tropica, including mitotic, meiotic and parasexual processes. It underpins the need for more genomic surveillance of Leishmania, to detect emerging hybrids that could spread more widely and to better understand the association between genetic variation and treatment outcome. Furthering our understanding of Leishmania genome evolution and ancestry will aid better diagnostics and treatment for cutaneous leishmaniasis caused by L.tropica in the Middle East. Author SummaryCutaneous leishmaniasis is mainly caused by Leishmania tropica in the Middle East, where it is known for treatment failure and a need for prolonged and/or multiple treatments. Several factors affect the clinical presentation and treatment outcome, such as host genetic variability and specific immune response, as well as environmental factors and the vector species. Little is known about the parasite genome and its influence on treatment response. By analysing the genome of 22 isolates of L. tropica, we have revealed extensive genomic variation and a complex population structure with evidence of genetic exchange within and among the isolates, indicating a possible presence of sexual or parasexual mechanisms. Understanding the Leishmania genome better may improve future treatment and better understanding of treatment failure and relapse.

genetics↗

bioRxiv2021

Distinct lung-homing receptor expression and activation profiles on NK cell and T cell subsets in COVID-19 and influenza

Respiratory viral infections with SARS-CoV-2 or influenza viruses commonly induce a strong infiltration of immune cells into the lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, little is known about how blood natural killer (NK) cells and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Using 28-colour flow cytometry and re-analysis of published RNA-seq datasets, we provide a detailed comparative analysis of NK cells and T cells in peripheral blood from moderately sick COVID-19 and influenza patients, focusing on the expression of chemokine receptors known to be involved in leukocyte recruitment to the lung. The results reveal a predominant role for CXCR3, CXCR6, and CCR5 in COVID-19 and influenza patients, mirrored by scRNA-seq signatures in peripheral blood and bronchoalveolar lavage from publicly available datasets. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation as compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza as compared to COVID-19. Together, our results indicate migration of functionally competent CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells to the lungs in moderate COVID-19 and influenza patients, identifying potential common targets for future therapeutic interventions in respiratory viral infections. Author summaryThe composition of in particular CXCR3+ and/or CXCR6+ NK cells and T cells is altered in peripheral blood upon infection with SARS-CoV-2 or influenza virus in patients with moderate disease. Lung-homing receptor-expression is biased towards phenotypically activated NK cells and T cells, suggesting a functional role for these cells co-expressing in particular CXCR3 and/or CXCR6 upon homing towards the lung.

immunology↗

bioRxiv2020

Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific antibodies are typically a major predictor of protective immunity, yet B cell and antibody responses during COVID-19 are not fully understood. Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) concentrations were higher in serum of patients who were hospitalized for longer, supporting the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and provides tools to study immune responses to SARS-CoV-2 infection and vaccination.

immunology↗