Green, C. A. | bioRxiv Science

bioRxiv2024

Differential control of mycobacteria among COVID-19 patients is associated with CD28+ CD8+ T cells

Diseases caused by SARS-CoV-2 and Mycobacterium tuberculosis (M.tb) represent two public health emergencies. In severe disease, both pathogens may share a biological niche in the lower respiratory tract. There is significant potential for SARS-CoV-2 and M.tb infections to be co-present within individuals and enhance or moderate the respective outcomes of either infection. Here, we investigated how whole blood samples, as well as CD4+ and CD8+ T cells, from individuals hospitalised with acute COVID-19 disease respond to mycobacterial challenge. To do this, samples were assessed by ex vivo mycobacterial growth inhibition assays, immune cell phenotyping by mass cytometry, and whole blood cytokine responses to mycobacterial antigens assessed by flow cytometry. These studies identified a subgroup of COVID-19 patients whose blood had an enhanced capacity to inhibit mycobacterial growth. The ability to control mycobacterial growth was associated with the presence of a non M.tb-specific CD28+ CD8+ T cell population, with a particular activation status and migratory phenotype. This work improves our understanding of factors involved in mycobacterial control, and may contribute to the design of novel therapies for TB.

immunology↗

bioRxiv2021

Organophosphate intoxication in C. elegans reveals a new route to mitigate poisoning through the modulation of determinants responsible for nicotinic acetylcholine receptor function

Plasticity is a reactive mechanism that allows the adaptation of organisms to changing environmental cues. The exploitation of this physiological process has a clear benefit to promote the recovery from a wide range of neurological disorders. Here, we show that plasticity-promoting regimes provide candidate mechanisms to supplement the classically used antidotes for anti-cholinesterase poisoning. These neurotoxins inhibit acetylcholinesterase, causing the overstimulation of cholinergic transmission at synapses and neuromuscular junctions. The model organism C. elegans exhibits organophosphate-induced mitigating plasticity that impacts on the recovery of neuromuscular phenotypes, initially impaired by the drug. This is underpinned by overstimulation of nicotinic receptors at the neuromuscular junction. Intrinsic determinants of receptors location and sensitivity modulate the extent of plasticity in the context of persistent cholinergic stimulation. Our results indicate that pharmacological intervention of nicotinic receptors and/or scaffolding proteins that support receptor function might provide a novel treatment route for anti-cholinesterase poisoning.

neuroscience↗

bioRxiv2018

Comprehensive profiling of antibodies against multiple infectious diseases in serum and the airway mucosa using synthetic peptide-based linear epitope microarrays

BackgroundDespite the considerable progress that has been achieved in the development of vaccines, infectious diseases continue to be the major cause of morbidity and mortality in developing countries. The first year of life remains the time of greatest risk with more than half of all deaths caused by infectious diseases in children under the age of five years occurring during this period. For most infections, antibodies are the strongest immune correlate of protective immunity and characterizing the breadth of the antibody repertoire against infectious diseases in early life is key to profiling individual disease risk.\n\nMethodsIn order to comprehensively profile the antibody repertoire against infectious diseases in early life, we developed a synthetic peptide-based microarray to simultaneously measure antibodies against forty one common infectious diseases. 82 empirically-validated linear B-cell epitopes were selected from the Immune Epitope Database (IEBD), expressed as synthetic peptides and printed onto microarray glass slides (microarray chip). The chip was used to simultaneously measure antigen-specific IgG and IgA in serum and mucosal samples from thirty eight infants and young children presenting to hospital with different illnesses. We also used the data from the microarray to estimate antibody decay kinetics for the five most frequently detected antigens during the first year of life.\n\nResultsA synthetic peptide microarray to measure antibodies against forty one infectious diseases was successfully developed. Although the combination of antigens that were recognized were different for each child, antigens derived from Epstein-Barr virus, poliovirus, Streptococcus pneumoniae, plasmodium falciparum and varicella zoster were recognized by most study participants. While the combination of antigens recognized in serum was generally similar as those recognized in mucosal samples, antibodies to antigens such as herpesvirus, rubella and echinococcus were more predominant in either serum or mucosal samples. With the exception of the pneumococcus, we observed a progressive decline in serum IgG specific to all the infections above in the first six months of life. Pneumococcal IgG in serum exhibited a continuous rise in the first six months of life.\n\nConclusionsWe successfully developed a synthetic peptide microarray and used it to profile the diversity of systemic and mucosal antibody against multiple infectious diseases in children. The data from the slide provide a snapshot overview of the breadth and kinetics of infectious disease antibodies early in life and opens the opportunity for conducting in-depth multi, multi-target serological studies of infectious diseases in future.

immunology↗