Tippalagama, R. | bioRxiv Science

bioRxiv2018

No cell is an island: circulating T cell:monocyte complexes are markers of immune perturbations

Our results highlight for the first time that a significant proportion of cell doublets in flow cytometry, previously believed to be the result of technical artefacts and thus ignored in data acquisition and analysis, are the result of true biological interaction between immune cells. In particular, we show that cell:cell doublets pairing a T cell and a monocyte can be directly isolated from human blood, and high resolution microscopy shows polarized distribution of LFA1/ICAM1 in many doublets, suggesting in vivo formation. Intriguingly, T cell:monocyte complex frequency and phenotype fluctuate with the onset of immune perturbations such as infection or immunization, reflecting expected polarization of immune responses. Overall these data suggest that cell doublets reflecting T cell-monocyte in vivo immune interactions can be detected in human blood and that the common approach in flow cytometry to avoid studying cell:cell complexes should be revisited.

immunology↗

bioRxiv2018

Emergence of a Dengue virus serotype 2 causing the largest ever dengue epidemic in Sri Lanka

BackgroundSri Lanka experienced the largest ever dengue outbreak in year 2017, which coincided with the shift of the predominant circulating dengue virus (DENV) 1 to DENV2 after 9 years. As it was felt that more patients appeared to develop complications and severe dengue, we compared clinical features of patients with acute dengue, with the previous circulating serotype (DENV1) and also sequenced the new virus, to determine the lineage of the virus.\n\nMethodology/Principal findingsWe studied the clinical and laboratory features of 172 adult patients with acute DENV1 (n=79) and DENV2 (n=93) infection. 65 (82.3%) of those with DENV1 and 86 (92.4%) of those with DENV2 were experiencing a secondary infection. The risk of developing dengue haemorrhagic fever (DHF) was significantly higher (=0.005, odds ratio=2.5) in those infected with DENV2 (54.8%) when compared to DENV1(32.9%), even though similar proportions of patients had a secondary dengue infection. Patients with DENV2 infection developed leakage significantly earlier (p<0.0001, median= 3, days) when compared to those with a DENV1 infection (median 5 days) and were more likely to develop significant bleeding and to require blood transfusions. Furthermore, patients with DENV2 were more likely to have significantly lower platelet counts during day 3, 4 and 5 since onset of illness.\n\nWhole genome sequencing showed that these DENV-2 isolates belonged to a cosmopolitan strain and was genetically more distant than the DENV-2 strains that circulated from 1981 to 2004 in Sri Lanka.\n\nConclusions/significanceSince this DENV2 strain appears to cause more severe forms of clinical disease, it would be important to determine variations in the virus genome or other factors that could have contributed to severe disease.\n\nAuthor summarySri Lanka experienced the largest ever dengue outbreak in year 2017, which coincided with the shift of the predominant circulating dengue virus (DENV) 1 to DENV2 after 9 years. We studied the clinical and laboratory features of 172 adult patients with acute DENV1 (n=79) and DENV2 (n=93) infection. The risk of developing dengue haemorrhagic fever was significantly higher (=0.005, odds ratio=2.5) in those infected with DENV2 (54.8%) when compared to DENV1(32.9%), even though similar proportions of patients had a secondary dengue infection. Patients with DENV2 infection developed leakage significantly earlier (p<0.0001, median= 3, days) when compared to those with a DENV1 infection (median 5 days) and were more likely to develop significant bleeding. Whole genome sequencing showed that these DENV-2 isolates belonged to cosmopolitan strain and was genetically more distant to the DENV-2 strains that circulated from 1981 to 2004 in Sri Lanka.

epidemiology↗