Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the ...polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV) in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
COVID-19 in Africa: Dampening the storm? Mbow, Moustapha; Lell, Bertrand; Jochems, Simon P ...
Science,
08/2020, Letnik:
369, Številka:
6504
Journal Article, Web Resource
Recenzirano
Odprti dostop
The dampened course of COVID-19 in Africa might reveal innovative solutions
Coronavirus disease 2019 (COVID-19) has spread rapidly and extensively to most countries in the world, resulting in ...considerable mortality in Europe and the United States, as well as in numerous upper-middle-income countries in South America and Asia. Experts predicted millions of COVID-19 deaths in Africa because many countries in the continent rank poorly on the United Nations Development Programme's Human Development Index. However, more than 4 months after the first cases in Africa were detected, prevalence and mortality are still low. It remains unclear if Africa is really spared from substantial cases and deaths. However, differences between Africa and the most affected countries in reliable reporting and death registration, lockdown stringency, demography, sociocultural aspects, environmental exposures, genetics, and the immune system could help to explain the experience of COVID-19 in Africa.
Respiratory viral infections frequently lead to severe respiratory disease, particularly in vulnerable populations such as young children, individuals with chronic lung conditions and older adults, ...resulting in hospitalisation and, in some cases, fatalities. The innate immune system plays a crucial role in monitoring for, and initiating responses to, viruses, maintaining a state of preparedness through the constant expression of antimicrobial defence molecules. Throughout the course of infection, innate immunity remains actively involved, contributing to viral clearance and damage control, with pivotal contributions from airway epithelial cells and resident and newly recruited immune cells. In instances where viral infections persist or are not effectively eliminated, innate immune components prominently contribute to the resulting pathophysiological consequences. Even though both young children and older adults are susceptible to severe respiratory disease caused by various respiratory viruses, the underlying mechanisms may differ significantly. Children face the challenge of developing and maturing their immunity, while older adults contend with issues such as immune senescence and inflammaging. This review aims to compare the innate immune responses in respiratory viral infections across both age groups, identifying common central hubs that could serve as promising targets for innovative therapeutic and preventive strategies, despite the apparent differences in underlying mechanisms.
Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas
. Novel medicines and vaccines are urgently needed
. ...An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3-10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4
T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.
Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving ...herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show that S. pneumoniae colonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance.
Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome ...composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium/Dolosigranulum-dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.
The morbidity and mortality related to respiratory tract diseases is enormous, with hundreds of millions of individuals afflicted and four million people dying each year. Understanding the ...immunological processes in the mucosa that govern outcome following pathogenic encounter could lead to novel therapies. There is a need to study responses at mucosal surfaces in humans for two reasons: (i) Immunological findings in mice, or other animals, often fail to translate to humans. (ii) Compartmentalization of the immune system dictates a need to study sites where pathogens reside. In this manuscript, we describe two novel non-invasive nasal mucosal microsampling techniques and their use for measuring immunological parameters: 1) using nasal curettes to collect cells from the inferior turbinate and; 2) absorptive matrices to collect nasal lining fluid. Both techniques were well tolerated and yielded reproducible and robust data. We demonstrated differences in immune populations and activation state in nasal mucosa compared to blood as well as compared to nasopharyngeal lumen in healthy adults. We also found superior cytokine detection with absorptive matrices compared to nasal wash. These techniques are promising new tools that will facilitate studies of the immunological signatures underlying susceptibility and resistance to respiratory infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Hookworm infection remains a significant public health concern, particularly in low- and middle-income countries, where mass drug administration has not stopped reinfection. Developing a ...vaccine is crucial to complement current control measures, which necessitates a thorough understanding of host immune responses. By leveraging controlled human infection models and high-dimensional immunophenotyping, here we investigated the immune remodeling following infection with 50 Necator americanus L3 hookworm larvae in four naïve volunteers over two years of follow-up and compared the profiles with naturally infected populations in endemic areas. Increased plasmacytoid dendritic cell frequency and diminished responsiveness to Toll-like receptor 7/8 ligand were observed in both controlled and natural infection settings. Despite the increased CD45RA + regulatory T cell (T regs ) frequencies in both settings, markers of T regs function, including inducible T-cell costimulatory (ICOS), tumor necrosis factor receptor 2 (TNFR2), and latency-associated peptide (LAP), as well as in vitro T regs suppressive capacity were higher in natural infections. Taken together, this study provides unique insights into the immunological trajectories following a first-in-life hookworm infection compared to natural infections.
Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain ...pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load.
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