Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the ...procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection. In 337 participants, BAL volume and BAL cell count were correlated in those with active TB disease, and current smokers. The right middle lobe yielded the highest volume. BAL cell and volume yields were lower in older participants, who also had more neutrophils. Current smokers yielded lower volumes and higher numbers of all cell types, and usually had a black pellet. Active TB disease was associated with higher cell yields, but this declined at the end of treatment. HIV infection was associated with more bloody pellets, and recent SARS-CoV-2 infection with a higher proportion of lymphocytes. These results allow researchers to optimise their participant and end assay selection for projects involving lung immune cells.
Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Characterised by the onset of hypertension and proteinuria in the second half of pregnancy, it can lead to maternal ...end-organ injury such as cerebral ischemia and oedema, pulmonary oedema and renal failure, and potentially fatal outcomes for both mother and fetus. The causes of the different maternal end-organ phenotypes of pre-eclampsia and why some women develop pre-eclampsia condition early in pregnancy have yet to be elucidated. Omics methods include proteomics, genomics, metabolomics, transcriptomics. These omics techniques, previously mostly used on bulk tissue and individually, are increasingly available at a single cellular level and can be combined with each other. Multi-omics techniques on a single-cell or spatial level provide us with a powerful tool to understand the pathophysiology of pre-eclampsia. This review will explore the status of omics methods and how they can and could contribute to understanding the pathophysiology of pre-eclampsia.
•The pathophysiology of pre-eclampsia and ist subtypes remains to be elucidated.•Various omics techniques are increasingly available on a single-cell and spatial level.•These novel techniques may help to better understand the pathophysiology of pre-eclampsia and its different phenotypes.
Pregnancy is dependent on the development of maternal immune tolerance to the genetically foreign fetus. During pregnancy the mother's immune reactivity and energy metabolism undergoes significant ...changes and the levels of certain hormones in peripheral blood are significantly increased. Hormones are important regulators of the functional activity of the immune system and immune cells within. Hormones secreted by the placenta, protect the fetus from the maternal immune response of the mother, emphasizing their immunomodulatory effects. Therefore, hormonal regulation is essential for the functional activity of immune cells. There is evidence that the hormone, kisspeptin, plays a role in the development of immune tolerance during pregnancy based on its role in the regulation of the adaptive T regulatory (aTreg)/T-helper 17 (Th17) cells, induction of the enzyme indoleamine 2,3-dioxygenase (IDO) and regulation of monocyte function during pregnancy. In addition, kisspeptin has been implicated in the regulation of specific cytokines during pregnancy. It is crucial to maintain an appropriate cytokine balance at the maternal– fetal interface as well as in circulation. Several pregnancy-related disorders have been associated with a variation in Th1/Th2/Th17 cytokines and aTreg cell subsets. Kisspeptin has been implicated in regulating cytokines IL-10 and IL-17A as well as aTreg and Th17 cells which are significant role players in immune tolerance during pregnancy. However, its effect on other pro- and anti-inflammatory cytokines remain unknown. Therefore, more research is required to better understand the role of kisspeptin in the development of immune tolerance during pregnancy. The hypothesis of this study is that kisspeptin alters the expression of anti-and pro-inflammatory cytokines and may thus influence the establishment of immune tolerance in pregnancy. To test this hypothesis, we used a previously established in vitro peripheral blood mononuclear cell (PBMC) Mycobacterium tuberculosis (Mtb) infection assay model as well as a newly established in vitro infection model using lipopolysaccharide (LPS)-stimulated whole blood. Protein expression analysis of selected pro- and anti-inflammatory cytokines was performed on PBMC infected with Mtb and on whole blood cells stimulated with LPS in the absence and presence of kisspeptin-10 for different times. The cytokines levels were measured by luminex multiplex assay and sandwich ELISA, respectively. Results from the PBMC infection assay showed a varied but not statistically significant effect of kisspeptin-10 on selected pro- and anti-inflammatory cytokine expression at 2 hours post-infection. However, there was a suggestion of an inhibitory effect of kisspeptin-10 on selected pro- and anti-inflammatory cytokine expression, macrophage inflammatory protein (MIP)-1α, MIP-1β, tumour necrosis factor (TNF)-α, granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-10, after 24 hours which was not observed at 6 days post-infection. Results from the whole blood stimulation assay suggested an inhibitory effect of kisspeptin-10 on selected LPS-induced pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) whilst generally not having an effect on selected anti-inflammatory cytokines (IL-10). Overall this study suggests, based on the lack of statistically significant data, a potential immunomodulatory effect of kisspeptin-10 based on the observed inhibition of pro-inflammatory cytokines. Investigating and developing an understanding of key regulators and mechanisms of maternal immune tolerance may help researchers understand the pathophysiological mechanisms underlying certain pregnancy-related disorders. This was a pilot study aimed at characterising the effect of kisspeptin stimulation on cytokines and chemokines responses. Manipulation of regulatory hormones such as kisspeptin could represent a potentially novel approach in the treatment of various pregnancy-related disorders including preeclampsia and unexplained recurrent miscarriage.
