scholarly journals Insights Into the Effects of Mucosal Epithelial and Innate Immune Dysfunction in Older People on Host Interactions With Streptococcus pneumoniae

2021 ◽  
Vol 11 ◽  
Author(s):  
Caroline M. Weight ◽  
Simon P. Jochems ◽  
Hugh Adler ◽  
Daniela M. Ferreira ◽  
Jeremy S. Brown ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Older People ◽  
Immune Cell ◽  
Herd Immunity ◽  
Pneumococcal Infection ◽  
Innate Immune ◽  
Older Individuals ◽  
Serotype Replacement ◽  
Pneumococcal Colonization ◽  
The Impact

In humans, nasopharyngeal carriage of Streptococcus pneumoniae is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together, these kill over 500,000 people over the age of 70 years worldwide every year. Pneumococcal conjugate vaccines have been largely successful in reducing IPD in young children and have had considerable indirect impact in protection of older people in industrialized country settings (herd immunity). However, serotype replacement continues to threaten vulnerable populations, particularly older people in whom direct vaccine efficacy is reduced. The early control of pneumococcal colonization at the mucosal surface is mediated through a complex array of epithelial and innate immune cell interactions. Older people often display a state of chronic inflammation, which is associated with an increased mortality risk and has been termed ‘Inflammageing’. In this review, we discuss the contribution of an altered microbiome, the impact of inflammageing on human epithelial and innate immunity to S. pneumoniae, and how the resulting dysregulation may affect the outcome of pneumococcal infection in older individuals. We describe the impact of the pneumococcal vaccine and highlight potential research approaches which may improve our understanding of respiratory mucosal immunity during pneumococcal colonization in older individuals.

scholarly journals Ageing alters the impact of nutrition on immune function

2016 ◽  
Vol 76 (3) ◽  
pp. 347-351 ◽  
Author(s):  
Parveen Yaqoob
Keyword(s):  
Older People ◽  
Immune Function ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Older Individuals ◽  
Age Related ◽  
Dietary Strategies ◽  
Future Work ◽  
The Impact ◽  
Result Interpretation

Immunosenescence during ageing is a major challenge which weakens the ability of older individuals to respond to infection or vaccination. There has been much interest in dietary strategies to improve immunity in older people, but there is an assumption that modulation of the immune response in older people will be based on the same principles as for younger adults. Recent evidence suggests that ageing fundamentally alters the impact of nutrition on immune function. As a result, interpretation of data from studies investigating the impact of diet on immune function is highly dependent on subject age. Study design is critically important when investigating the efficacy of dietary components, and most studies involving older people include rigorous inclusion/exclusion criteria based on medical history, laboratory tests, general health status and often nutritional status. However, immunological status is rarely accounted for, but can vary significantly, even amongst healthy older people. There are several clear examples of age-related changes in immune cell composition, phenotype and/or function, which can directly alter the outcome of an intervention. This review uses two case studies to illustrate how the effects of n-3 PUFA and probiotics differ markedly in young v. older subjects. Evidence from both suggests that baseline differences in immunosenescence influence the outcome of an intervention, highlighting the need for detailed immunological characterisation of subjects prior to interventions. Finally, future work elucidating alterations in metabolic regulation within cells of the immune system as a result of ageing may be important in understanding the impact of diet on immune function in older people.

scholarly journals 2714. Streptococcus pneumoniae Nasopharyngeal Carriage in Canadian Adults Hospitalized with Community-Acquired Pneumonia from 2010 to 2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S954-S955
Author(s):  
Jason J LeBlanc ◽  
May ElSherif ◽  
Amanda L S Lang ◽  
Hayley D Gillis ◽  
Lingyun Ye ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Real Time ◽  
Herd Immunity ◽  
Community Acquired Pneumonia ◽  
Serotype Distribution ◽  
Childhood Immunization ◽  
Vaccine Serotypes ◽  
Serotype Replacement ◽  
The Impact ◽  
Over Time

Abstract Background Streptococcus pneumoniae can colonizes the human nasopharynx, and can cause life-threatening infections like community-acquired pneumonia (CAP) and invasive pneumococcal diseases (IPD). In Canada, the 13-valent conjugate vaccine (PCV13) was introduced in childhood immunization since 2010, with hopes that it would not only protect the vaccinated, but also confer indirect protection to adults through herd immunity. Given data on S. pneumoniae nasopharyngeal (NP) carriage in adults is scarce, this study reports on S. pneumoniae-positivity and serotype distribution in adult carriage from years 2010 to 2017. Methods Active surveillance was performed in adults hospitalized with for CAP or IPD from December 2010 to 2017. For assessment of S. pneumoniae carriage, NP swabs were tested using lytA and cpsA real-time PCR. S. pneumoniae-positive NPs were subjected to serotyping using conventional and real-time multiplex PCRs. Results Overall, 6472 NP swabs were tested, and Spn was identified in 366 (5.7%). Of the 366 S. pneumoniae-positive NP swabs, a serotype was assigned in 355 (97.0%). From years 2010 to 2017, the proportion of S. pneumoniae-positive NP swabs declined from 8.9% to 4.3%. This was also reflected in the proportion of serotypeable results attributed to PCV13 serotypes, which also declined from 76.9% to 42.2%. The decline was primarily attributed to PCV13 serotypes 7F and 19A. PCV13 serotype 3 remained predominant throughout the study, as did non-PCV13 serotypes like 22F, 33F, and 11A. On the other hand, a proportional rise over time was noted for non-vaccine serotypes (from 15.4% to 31.1%). This was primarily attributed to serotypes 23A, 15A, and 35B. Conclusion Monitoring serotype trends is important to assess the impact of pneumococcal vaccines. While herd immunity from PCV13 childhood immunization was anticipated, few studies have assessed its impact on adult carriage. This study described Spn serotype distribution in adults over years 2010 to 2017, demonstrating not only a reduction of PCV13 serotypes over time, but a proportional rise in non-vaccine serotypes. These emerging serotypes may represent the emergence of serotype replacement. Ongoing serotype surveillance will be needed to compare S. pneumoniae carriage to serotypes associated with pneumococcal CAP and IPD. Disclosures All authors: No reported disclosures.

scholarly journals The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

2021 ◽  
Vol 9 (6) ◽  
pp. 1324
Author(s):  
Fernanda Raya Tonetti ◽  
Mikado Tomokiyo ◽  
Ramiro Ortiz Moyano ◽  
Sandra Quilodrán-Vega ◽  
Hikari Yamamuro ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Innate Immune Response ◽  
Pneumococcal Infection ◽  
Innate Immune ◽  
Nasal Administration ◽  
Commensal Bacterium ◽  
Beneficial Effects ◽  
Immunological Mechanisms ◽  
Immunomodulatory Properties

Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

scholarly journals The Impact of Childhood Obesity on Inflammation, Innate Immune Cell Frequency, and Metabolic MicroRNA Expression

2014 ◽  
Vol 99 (3) ◽  
pp. E474-E478 ◽  
Author(s):  
Eirin Carolan ◽  
Andrew E. Hogan ◽  
Michelle Corrigan ◽  
Gadintshware Gaotswe ◽  
Jean O'Connell ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Immune Cell ◽  
Microrna Expression ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Cell Frequency ◽  
The Impact

scholarly journals A simulation study on the relative role of age groups under differing pertussis transmission scenarios

2018 ◽  
Author(s):  
Ana I. Bento ◽  
Aaron A. King ◽  
Pejman Rohani
Keyword(s):  
Herd Immunity ◽  
Age Groups ◽  
Transmission Model ◽  
Relative Role ◽  
Older Individuals ◽  
Age Cohorts ◽  
Relative Risks ◽  
Transmission Mechanisms ◽  
Acellular Vaccines ◽  
The Impact

AbstractPertussis has resurged in many countries where it was once regarded as under control, with the recent outbreaks showing a shift in incidence towards teens and older individuals. Here, using an age-stratified transmission model, we tested two potential causes for underlying changes in pertussis transmission dynamics. We did so assuming hypothesized mechanisms supporting present-day pertussis epidemiology: (I) improved diagnostics, (II) acellular vaccines leading to asymptomatic transmission (III) both. We used the relative risks and odds ratio methods to examine the impact of these differing assumptions on signatures of relative roles of key age groups through time, allowing us to explore those age cohorts that disproportionately account for transmission. Our findings show that for epidemics after the vaccine switch, a scenario with increased adult reporting and no asymptomatic transmission reflect a loss of signal, where no age group appears to be key. While scenarios with asymptomatic transmission, reflect a population where children (1-10 years old) are still disproportionally at risk. These results demonstrate that understanding the underlying transmission mechanisms in a population are paramount for vaccination policies in attaining herd immunity and eventually eradication.

scholarly journals The impact of specific and non-specific immunity on the ecology of Streptococcus pneumoniae and the implications for vaccination

2013 ◽  
Vol 280 (1771) ◽  
pp. 20131939 ◽  
Author(s):  
Stefan Flasche ◽  
W. John Edmunds ◽  
Elizabeth Miller ◽  
David Goldblatt ◽  
Chris Robertson ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Herd Immunity ◽  
Competitive Pressure ◽  
Deterministic Models ◽  
Universal Vaccine ◽  
Specific Immunity ◽  
Pneumococcal Carriage ◽  
Individual Based Simulation ◽  
Underlying Mechanisms ◽  
The Impact

More than 90 capsular serotypes of Streptococcus pneumoniae coexist despite competing for nasopharyngeal carriage and a gradient in fitness. The underlying mechanisms for this are poorly understood and make assessment of the likely population impact of vaccination challenging. We use an individual-based simulation model to generalize widely used deterministic models for pneumococcal competition and show that in these models short-term serotype-specific and serotype non-specific immunity could constitute the mechanism governing between-host competition and coexistence. We find that non-specific immunity induces between-host competition and that serotype-specific immunity limits a type's competitive advantage and allows stable coexistence of multiple serotypes. Serotypes carried at low prevalence show high variance in carriage levels, which would result in apparent outbreaks if they were highly pathogenic. Vaccination against few serotypes can lead to elimination of the vaccine types and induces replacement by others. However, in simulations where the elimination of the targeted types is achieved only by a combination of vaccine effects and the competitive pressure of the non-vaccine types, a universal vaccine with similar-type-specific effectiveness can fail to eliminate pneumococcal carriage and offers limited herd immunity. Hence, if vaccine effects are insufficient to control the majority of serotypes at the same time, then exploiting the competitive pressure by selective vaccination can help control the most pathogenic serotypes.

scholarly journals Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

2016 ◽  
Vol 84 (5) ◽  
pp. 1536-1547 ◽  
Author(s):  
Pamela Shen ◽  
Mathieu C. Morissette ◽  
Gilles Vanderstocken ◽  
Yang Gao ◽  
Muhammad Hassan ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Cigarette Smoke ◽  
Invasive Pneumococcal Disease ◽  
Bacterial Infections ◽  
Pneumococcal Disease ◽  
Pneumococcal Infection ◽  
Cigarette Smoke Exposure ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Pneumococcal Colonization

Streptococcus pneumoniaeis a leading cause of invasive bacterial infections, with nasal colonization an important first step in disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, the underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteremia and meningitis without prior lung infection. Mechanistically, deficiency in interleukin 1α (IL-1α) or platelet-activating factor receptor (PAFR), an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil-recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remains high worldwide, these findings are relevant to the continued efforts to reduce the invasive pneumococcal disease burden.

scholarly journals Rationing care by frailty during the COVID-19 pandemic

2020 ◽  
Author(s):  
Emma Grace Lewis ◽  
Matthew Breckons ◽  
Richard P Lee ◽  
Catherine Dotchin ◽  
Richard Walker
Keyword(s):  
Critical Care ◽  
Older People ◽  
Adverse Outcome ◽  
Older Individuals ◽  
Short Term ◽  
Clinical Frailty Scale ◽  
Widespread Implementation ◽  
Care Outcomes ◽  
Resource Allocation Strategy ◽  
The Impact

Abstract The coronavirus disease 2019 (COVID-19) pandemic is disproportionately affecting older people and those with underlying comorbidities. Guidelines are needed to help clinicians make decisions regarding appropriate use of limited NHS critical care resources. In response to the pandemic, the National Institute for Health and Care Excellence published guidance that employs the Clinical Frailty Scale (CFS) in a decision-making flowchart to assist clinicians in assessing older individuals’ suitability for critical care. This commentary raises some important limitations to this use of the CFS and cautions against the potential for unintended impacts. The COVID-19 pandemic has allowed the widespread implementation of the CFS with limited training or expert oversight. The CFS is primarily being used to assess older individuals’ risk of adverse outcome in critical care, and to ration access to care on this basis. While some form of resource allocation strategy is necessary for emergencies, the implementation of this guideline in the absence of significant pressure on resources may reduce the likelihood of older people with frailty, who wish to be considered for critical care, being appropriately considered, and has the potential to reinforce the socio-economic gradient in health. Our incomplete understanding of this novel disease means that there is a need for research investigating the short-term predictive abilities of the CFS on critical care outcomes in COVID-19. Additionally, a review of the impact of stratifying older people by CFS score as a rationing strategy is necessary in order to assess its acceptability to older people as well as its potential for disparate impacts.

scholarly journals The Impact of Communication Technology and Social Media on Intergenerational Relationships between Older Individuals and Their Adult Children in Bangkok

MANUSYA ◽  
2020 ◽  
Vol 23 (2) ◽  
pp. 188-204
Author(s):  
Marie-Helene Thomas
Keyword(s):  
Social Media ◽  
Older People ◽  
Communication Technology ◽  
Adult Children ◽  
Instant Messaging ◽  
Smart Phone ◽  
Intergenerational Relationships ◽  
Older Individuals ◽  
Intergenerational Relationship ◽  
The Impact

Modernisation theory (Cowgill and Holmes 1972) argues that older people in modern societies are less respected and valued as a result of technological innovations. To understand the impact of communication technology and social media on Thai society, this research studies the transformations in communication, interaction and overall connectedness between older people and their adult children. In addition, it examines what elements have shifted due to the introduction and use of the smart phone and its accompanying instant messaging and social media applications such as Line and Facebook. The data demonstrates various positive and negative impacts on the intergenerational relationship between older parents and their child cohorts. Crucially, countless examples and arguments from the respondents suggest that the use of these new tools of communication has a very real and demonstrable impact, from providing a space for family members to express their emotions to being the culprit that divides the family unit.

scholarly journals Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms

2021 ◽  
Vol 5 ◽  
pp. 286
Author(s):  
Fiona Sargison ◽  
Mariya I Goncheva ◽  
Joana Alves ◽  
Amy Pickering ◽  
J Ross Fitzgerald
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Blood ◽  
Immune Cell ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Bacterial Killing ◽  
Isogenic Mutant ◽  
Extracellular Milieu ◽  
The Impact

Background: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown. Methods: We employed the epidemic S. aureus clone USA300 strain LAC and its lipase deficient isogenic mutant, along with recombinant lipase proteins, in in vitro experimental infection assays. To determine if lipases can inhibit innate immune killing mechanisms, the bactericidal activity of whole blood, human neutrophils, and macrophages was analysed. In addition, gentamycin protection assays were carried out to examine the influence of lipases on S. aureus innate immune cell escape. Results: There were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases. Conclusions: S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. These findings broaden our understanding of the interaction of S. aureus with the innate immune system.

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