Mechanisms Driving Macrophage Diversity and Specialization in Distinct Tumor Microenvironments and Parallelisms with Other Tissues

Macrophages are extremely versatile cells that adopt a distinct phenotype in response to a changing microenvironment. Consequently, macrophages are involved in diverse functions, ranging from organogenesis and tissue homeostasis to recognition and destruction of invading pathogens. In cancer, tumor-associated macrophages (TAM) often contribute to tumor progression by increasing cancer cell migration and invasiveness, stimulating angiogenesis, and suppressing anti-tumor immunity. Accumulating evidence suggests that these different functions could be exerted by specialized TAM subpopulations. Here, we discuss the potential underlying mechanisms regulating TAM specialization and elaborate on TAM heterogeneity in terms of their ontogeny, activation state, and intra-tumoral localization. In addition, parallels are drawn between TAM and macrophages in other tissues. Together, a better understanding of TAM diversity could provide a rationale for novel strategies aimed at targeting the most potent tumor-supporting macrophages

Community-informed research on malaria in pregnancy in Monrovia, Liberia: a grounded theory study

Background: Liberia is a West African country that needs substantial investment to strengthen its National Malaria Control Programme (NMCP), which was disrupted during the 2014–2016 Ebola epidemic. As elsewhere, Liberian pregnant women are especially vulnerable to malaria. Understanding prevention and treatment-seeking behaviours among the population is crucial to strategize context-specifc and women-centred actions, including locally-led malaria research, to improve women’s demand, access and use of NMCP strategies against malaria in pregnancy. Methods: In 2016, after the Ebola crisis, a qualitative inquiry was conducted in Monrovia to explore populations’ insights on the aetiology, prevention and therapeutics of malaria, as well as the community and health workers’ perceptions on the utility of malaria research for pregnant women. In-depth interviews and focus group discussions were conducted among pregnant women, traditional community representatives and hospital staf (n=38), using a feminist interpretation of grounded theory. Results: The narratives indicate that some Liberians believed in elements other than mosquito bites as causes of malaria; many had a low malaria risk perception and disliked current efective prevention methods, such as insecticide-treated nets; and some would resort to traditional medicine and spiritual care to cure malaria. Access to clinic-based malaria care for pregnant women was reportedly hindered by lack of fnancial means, by unofcial user fees requested by healthcare workers, and by male partners’ preference for traditional medicine. The participants suggested that malaria research in Liberia could help to design evidence-based education to change current malaria prevention, diagnostic and treatment-seeking attitudes, and to develop more acceptable prevention technologies. Conclusion: Poverty, insufcient education on malaria, corruption, and poor trust in healthcare establishment are structural factors that may play a greater role than local traditional beliefs in deterring Liberians from seeking, access‑ ing and using government-endorsed malaria control strategies. To increase access to and uptake of preventive and biomedical care by pregnant women, future malaria research must be informed by people’s expressed needs and constructed meanings and values on health, ill health and healthcare

Training through malaria research: building capacity in good clinical and laboratory practice in Liberia

Background: Limited health research capacities (HRC) undermine a country’s ability to identify and adequately respond to local health needs. Although numerous interventions to strengthen HRC have been conducted in Africa, there is a need to share the lessons learnt by funding organizations, institutes and researchers. The aim of this report is to identify best practices in HRC strengthening by describing a training programme conducted between 2016 and 2017 at the Saint Joseph’s Catholic Hospital (SJCH) in Monrovia (Liberia). Methods: A call for trainees was launched at the SJCH, the Liberia Medicines and Health Products Regulatory Author‑ ity (LMHRA), the Ministry of Health and Social Welfare, the Mother Pattern College of Health Sciences (MPCHS) and community members. Selected trainees participated in four workshops on Good Clinical Laboratory Practice (GCLP), standard operating procedures (SOP) and scientifc communication, as well as in a 5-months eLearning mentoring programme. After the training, a collectively-designed research project on malaria was conducted. Results: Twenty-one of the 28 trainees (14 from the SJCH, 3 from LMHRA, one from MPCHS, and 10 community representatives) completed the programme satisfactorily. Pre- and post-training questionnaires completed by 9 of the trainees showed a 14% increase in the percentage of correct answers. Trainees participated in a mixed-methods crosssectional study of Plasmodium falciparum infection among pregnant women at the SJCH. Selected trainees dissemi‑ nated activities and research outcomes in three international meetings and three scientifc publications. Conclusion: This training-through-research programme successfully involved SJCH staf and community members in a practical research exercise on malaria during pregnancy. The challenge is to ensure that the SJCH remains active in research. Harmonization of efectiveness indicators for HRC initiatives would strengthen the case for investing in such eforts

What do we know about Immunity to SARS-CoV-2? Implications for Public Health Policies

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóAs the COVID-19 pandemic progresses, so does our knowledge of the magnitude, type and durability of the immune response to SARS-CoV-2 as a result of natural infection or vaccination. This information is crucial since it will largely define the strategies we need to implement in order to protect individuals and populations. With this in mind, the GCMSC presents its second report, where they review the current knowledge on immunity to SARS-CoV-2 and the implications in terms of public health policies

Human CD6 down-modulation following T-Cell activation compromises lymphocyte survival and proliferative responses

Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3- (Tact) and FoxP3+ (Treg) T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+) or effector memory (effector memory T cell, CD45RA-CCR7-) phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA-CCR7+) counterparts. CD6lo/- T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses

Post-Acute COVID Syndrome (PACS): Definition, Impact and Management

Additional support from ISGlobal’s Antoni Plasència and Josep M. AntóA variety of studies suggest that up to 10-15% of all patients with COVID-19 may present persistent symptomatology weeks or even months after the original infection. Given the accumulated burden of COVID-19 in Catalonia, Spain, we speculate that over 90,000 patients could have been or are currently affected by persistent symptoms or sequelae. The Multidisciplinary Collaborative Group for the Scientific Monitoring of COVID-19 (GCMSC) presents its third report where they propose a clear set of case definitions of Post-Acute COVID syndrome (PACS) and its sub-categories and recommend a comprehensive medical examination to characterise the clinical features and complications when assessing PACS

Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses

Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3− (Tact) and FoxP3+ (Treg) T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+) or effector memory (effector memory T cell, CD45RA−CCR7−) phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA−CCR7+) counterparts. CD6lo/− T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses