Translational Potential of Therapeutics Targeting Regulatory Myeloid Cells in Tuberculosis

Despite recent advances in tuberculosis (TB) drug development and availability, successful antibiotic treatment is challenged by the parallel development of antimicrobial resistance. As a result, new approaches toward improving TB treatment have been proposed in an attempt to reduce the high TB morbidity and mortality rates. Host-directed therapies (HDTs), designed to modulate host immune components, provide an alternative approach for improving treatment outcome in both non-communicable and infectious diseases. Many candidate immunotherapeutics, designed to target regulatory myeloid immune components in cancer, have so far proven to be of value as repurposed HDT in TB. Several of these studies do however lack detailed description of the mechanism or host pathway affected by TB HDT treatment. In this review, we present an argument for greater appreciation of the role of regulatory myeloid cells, such as myeloid-derived suppressor cells (MDSC), as potential targets for the development of candidate TB HDT compounds. We discuss the role of MDSC in the context of Mycobacterium tuberculosis infection and disease, focussing primarily on their specific cellular functions and highlight the impact of HDTs on MDSC frequency and function

Higher SARS-CoV-2 seroprevalence in workers with lower socioeconomic status in Cape Town, South Africa.

BackgroundInequality is rife throughout South Africa. The first wave of COVID-19 may have affected people in lower socioeconomic groups worse than the affluent. The SARS-CoV-2 seroprevalence and the specificity of anti-SARS-CoV-2 antibody tests in South Africa is not known.MethodsWe tested 405 volunteers representing all socioeconomic strata from the workforce of a popular shopping and tourist complex in central Cape Town with the Abbott SARS-CoV-2 IgG assay. We assessed the association between antibody positivity and COVID-19 symptom status, medical history, and sociodemographic variables. We tested 137 serum samples from healthy controls collected in Cape Town prior to the COVID-19 pandemic, to confirm the specificity of the assay in the local population.ResultsOf the 405 volunteers tested one month after the first peak of the epidemic in Cape Town, 96(23.7%) were SARS-CoV-2 IgG positive. Of those who tested positive, 46(47.9%) reported no symptoms of COVID-19 in the previous 6 months. Seropositivity was significantly associated with living in informal housing, residing in a subdistrict with low income-per household, and having a low-earning occupation. The specificity of the assay was 98.54%(95%CI 94.82%-99.82%) in the pre-COVID controls.ConclusionsThere is a high background seroprevalence in Cape Town, particularly in people of lower socioeconomic status. Almost half of cases are asymptomatic, and therefore undiagnosed by local testing strategies. These results cannot be explained by low assay specificity

Blood transcriptomic signatures for symptomatic TB in an African multi-cohort study: Public, subject-level signature scores, RT-qPCR data, and metadata

Here we provide the public, subject-level datasets containing key variables necessary to reconstruct findings from the ScreenTB and AE-TBC sub-studies aimed at evaluating the diagnostic performance of multiple parsimonious transcriptomic signatures. A data dictionary is provided below.Gene expression of 20 transcriptomic signatures was measured in study participants from study sites located in six different African countries where the ScreenTB and AE-TBC studies were conducted. Gene expression data was generated from microfluidic RT-qPCR runs on mRNA derived from whole blood collected in PAXgene tubes. All results were verified before delta Ct values were calculated and used to compute signature scores.The public dataset for the sub-study is divided into (1) subject-level signature scores, (2) subject-level TaqMan RT-qPCR primer-probe assay raw cycle threshold (CT) gene expression data from the Standard BioTools microfluidic gene expression integrated fluidic circuits, and (3) subject-level metadata.</p