scholarly journals Development of Systemic Immune Dysregulation in a Rat Trauma Model with Biomaterial-Associated Infection

2020 ◽  
Author(s):  
Casey E. Vantucci ◽  
Hyunhee Ahn ◽  
Mara L. Schenker ◽  
Pallab Pradhan ◽  
Levi B. Wood ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Dysregulation ◽  
Hardware Failure ◽  
Orthopedic Injuries ◽  
Segmental Bone ◽  
Trauma Model ◽  
Orthopedic Infection ◽  
The Impact ◽  
Orthopedic Biomaterial

ABSTRACTOrthopedic biomaterial-associated infections remain a large clinical challenge, particularly with open fractures and segmental bone loss. Invasion and colonization of bacteria within immune-privileged canalicular networks of the bone can lead to local, indolent infections that can persist for years without symptoms before eventual catastrophic hardware failure. Host immunity is essential for bacterial clearance and an appropriate healing response, and recent evidence has suggested an association between orthopedic trauma and systemic immune dysregulation and immunosuppression. However, the impact of a local infection on this systemic immune response and subsequent effects on the local response is poorly understood and has not been a major focus for addressing orthopedic injuries and infections. Therefore, this study utilized a model of orthopedic biomaterial-associated infection to investigate the effects of infection on the long-term immune response. Here, despite persistence of a local, indolent infection lacking outward symptoms, there was still evidence of long-term immune dysregulation with systemic increases in MDSCs and decreases in T cells compared to non-infected trauma. Further, the trauma only group exhibited a regulated and coordinated systemic cytokine response, which was not present in the infected trauma group. Locally, the infection group had attenuated macrophage infiltration in the local soft tissue compared to the non-infected group. Our results demonstrate widespread impacts of a localized orthopedic infection on the systemic and local immune responses. Characterization of the immune response to orthopedic biomaterial-associated infection may identify key targets for immunotherapies that could optimize both regenerative and antibiotic interventions, ultimately improving outcomes for these patients.

The impact of Vaccination worldwide on SARS-CoV-2 infection: A Review on Vaccine Mechanisms, Results of Clinical Trials, Vaccinal Coverage and Interactions with Novel Variants

2021 ◽  
Vol 28 ◽  
Author(s):  
Douglas Henrique Pereira Damasceno ◽  
Arthur Aguiar Amaral ◽  
Cecília Andrade Silva ◽  
Ana Cristina Simões e Silva
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Placebo Group ◽  
Mechanisms Of Action ◽  
Novel Variants ◽  
The Impact ◽  
Positive Results ◽  
Epidemiological Information ◽  
Long Term Studies

Background: The COVID-19 pandemic demanded a global effort towards quickly developing safe and effective vaccines against SARS-CoV-2. Objective: This review aimed to discuss the main vaccines available, their mechanisms of action, results of clinical trials and epidemiological behavior. The implications of viral variants were also debated. Methods: A non-systematic literature review was performed between February and March 2021 by searching the Pubmed, Scopus, and SciELO databases, using different combinations of the following terms: "vaccines", "clinical trials" , "SARS-CoV-2", "Coronavirus", "COVID-19", "mechanisms of action". Data regarding clinical trials of SARS-CoV-2 vaccines and epidemiological information were also searched. Results: The mechanisms of action included vector-virus, mRNA and inactivated virus vaccines. The vaccines showed positive results in phases 2/3 clinical trials. The efficacy of the mRNA 1273 and of mRNA BNT 162b2 vaccines were 94.1% and 95%, respectively. The effectiveness of the ChAdOx1 nCoV-19 vaccine varied according to the scheme, with an overall value of 70.4%. The Gam-COVID-Vac vaccine had an efficacy of 91.6%. Regarding the Ad26.COV2.S vaccine, 99% or more of seroconversion was observed in all subgroups 29 days after vaccination. The CoronaVac vaccine induced an immune response in 92% of the volunteers receiving 3ug and in 98% with 6ug, in comparison to 3% in the placebo group. Conclusion: Global efforts have resulted in vaccines available in record time, with good safety and immunogenicity profile. However, only long-term studies can provide more information on duration of immunity and the need for additional doses.

scholarly journals Intestinal Explant Cultures from Gilthead Seabream (Sparus aurata, L.) Allowed the Determination of Mucosal Sensitivity to Bacterial Pathogens and the Impact of a Plant Protein Diet

2020 ◽  
Vol 21 (20) ◽  
pp. 7584
Author(s):  
David Sánchez Peñaranda ◽  
Christine Bäuerl ◽  
Ana Tomás-Vidal ◽  
Miguel Jover-Cerdá ◽  
Guillem Estruch ◽  
...  
Keyword(s):  
Immune Response ◽  
Phase Ii ◽  
Plant Protein ◽  
Gilthead Seabream ◽  
Growth Stages ◽  
Short Term ◽  
Short Term Exposure ◽  
Cox 2 ◽  
The Impact

The interaction between diet and intestinal health has been widely discussed, although in vivo approaches have reported limitations. The intestine explant culture system developed provides an advantage since it reduces the number of experimental fish and increases the time of incubation compared to similar methods, becoming a valuable tool in the study of the interactions between pathogenic bacteria, rearing conditions, or dietary components and fish gut immune response. The objective of this study was to determine the influence of the total substitution of fish meal by plants on the immune intestinal status of seabream using an ex vivo bacterial challenge. For this aim, two growth stages of fish were assayed (12 g): phase I (90 days), up to 68 g, and phase II (305 days), up to 250 g. Additionally, in phase II, the effects of long term and short term exposure (15 days) to a plant protein (PP) diet were determined. PP diet altered the mucosal immune homeostasis, the younger fish being more sensitive, and the intestine from fish fed short-term plant diets showed a higher immune response than with long-term feeding. Vibrio alginolyticus (V. alginolyticus) triggered the highest immune and inflammatory response, while COX-2 expression was significantly induced by Photobacterium damselae subsp. Piscicida (P. damselae subsp. Piscicida), showing a positive high correlation between the pro-inflammatory genes encoding interleukin 1β (IL1-β), interleukin 6 (IL-6) and cyclooxygenase 2(COX-2).

scholarly journals A Dual Infection/Competition Assay Shows a Correlation between Ex Vivo Human Immunodeficiency Virus Type 1 Fitness and Disease Progression

2000 ◽  
Vol 74 (19) ◽  
pp. 9222-9233 ◽  
Author(s):  
Miguel E. Quiñones-Mateu ◽  
Sarah C. Ball ◽  
Andre J. Marozsan ◽  
Vincent S. Torre ◽  
Jamie L. Albright ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Ex Vivo ◽  
Relative Fitness ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACT This study was designed to examine the impact of human immunodeficiency virus type 1 (HIV-1) fitness on disease progression through the use of a dual competition/heteroduplex tracking assay (HTA). Despite numerous studies on the impact of HIV-1 diversity and HIV-specific immune response on disease progression, we still do not have a firm understanding of the long-term pathogenesis of this virus. Strong and early CD8-positive cytotoxic T-cell and CD4-positive T-helper cell responses directed toward HIV-infected cells appear to curb HIV pathogenesis. However, the rate at which the virus infects the CD4+ T-cell population and possibly destroys the HIV-specific immune response may also alter the rate of disease progression. For HIV-1 fitness studies, we established conditions for dual HIV-1 infections of peripheral blood mononuclear cells (PBMC) and a sensitive HTA to measure relative virus production. A pairwise comparison was then performed to estimate the relative fitness of various non-syncytium-inducing/CCR5-tropic (NSI/R5) and syncytium-inducing/CXCR4-tropic (SI/X4) HIV-1 isolates. Four HIV-1 strains (two NSI/R5 and two SI/X4) with moderate ex vivo fitness were then selected as controls and competed against primary HIV-1 isolates from an HIV-infected Belgian cohort. HIV-1 isolates from long-term survivors (LTS) were outcompeted by control strains and were significantly less fit than HIV-1 isolates from patients with accelerated progression to AIDS (PRO). In addition, NSI/R5 HIV-1 isolates from PRO overgrew control SI/X4 strains, suggesting that not all SI/X4 HIV-1 isolates replicate more efficiently than all NSI/R5 isolates. Finally, there were strong, independent correlations between viral load and the total relative fitness values of HIV-1 isolates from PRO (r = 0.84, P = 0.033) and LTS (r = 0.86, P = 0.028). Separation of the PRO and LTS plots suggest that HIV-1 fitness together with viral load may be a strong predictor for the rate of disease progression.

Moraxella catarrhalisinduces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure

2015 ◽  
Vol 309 (3) ◽  
pp. L250-L261 ◽  
Author(s):  
Birgitt Gutbier ◽  
Katja Fischer ◽  
Jan-Moritz Doehn ◽  
Carolin von Lachner ◽  
Christian Herr ◽  
...  
Keyword(s):  
Immune Response ◽  
Systemic Inflammation ◽  
Bacterial Colonization ◽  
Smoke Exposure ◽  
Chronic Obstructive ◽  
Wild Type ◽  
Obstructive Pulmonary Disease ◽  
Lower Airways ◽  
The Impact

In patients with chronic obstructive pulmonary disease (COPD), Moraxella catarrhalis infection of the lower airways is associated with chronic colonization and inflammation during stable disease and acute exacerbations. Chronic smoke exposure induces chronic inflammation and impairs mucociliary clearance, thus contributing to bacterial colonization of the lower airways in COPD patients. The human-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5, expressed in human airways, has been shown to contribute to epithelial colonization of CEACAM-binding pathogens. To investigate the impact of CEACAM5 expression on pulmonary M. catarrhalis colonization, we infected mice transgenic for human CEACAM5 (hCEACAM5) and wild type mice intratracheally with M. catarrhalis with or without preceding smoke exposure and analyzed bacterial colonization and local and systemic inflammation. Our results show that airway infection with M. catarrhalis accelerated acute local but not systemic inflammation, albeit independent of hCEACAM5 expression. Long-term smoke exposure alone or prior to M. catarrhalis infection did not contribute to increased local or systemic inflammation. No difference was found in pulmonary clearance of M. catarrhalis in hCEACAM5-transgenic mice compared with wild-type mice. Smoke exposure neither altered time nor extent of persistence of M. catarrhalis in the lungs of both genotypes. In conclusion, M. catarrhalis induced a local acute immune response in murine airways. Neither hCEACAM5 expression nor chronic smoke exposure nor a combination of both was sufficient as prerequisites for the establishment of chronic M. catarrhalis colonization. Our results demonstrate the difficulties in mirroring conditions of chronic airways colonization of M. catarrhalis in a murine model.

scholarly journals Infection as a Stroke Risk Factor and Determinant of Outcome After Stroke

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 3156-3168 ◽  
Author(s):  
Mitchell S.V. Elkind ◽  
Amelia K. Boehme ◽  
Craig J. Smith ◽  
Andreas Meisel ◽  
Marion S. Buckwalter
Keyword(s):  
Stroke Risk ◽  
Respiratory Infections ◽  
Immune Dysregulation ◽  
Future Research ◽  
Cumulative Number ◽  
Stroke Risk Factor ◽  
Acute Infections ◽  
The Impact

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.

scholarly journals Intestinal Explant Cultures from Gilthead Seabream (Sparus Aurata, L.) Allowed Determining the Mucosal Sensitivity to Bacterial Pathogens and the Impact of a Plant Protein Diet

2020 ◽  
Author(s):  
David Sanchez Peñaranda ◽  
Christine Bäuerl ◽  
Ana Tomás-Vidal ◽  
Jover-Cerdá Miguel ◽  
Guillem Estruch ◽  
...  
Keyword(s):  
Immune Response ◽  
Phase Ii ◽  
Fish Meal ◽  
Ex Vivo ◽  
Innate Immune ◽  
Plant Protein ◽  
Bacterial Challenge ◽  
Short Term ◽  
The Impact

Abstract BackgroundAlthough high levels of fish meal replacement by alternative protein sources have been achieved without relevant alterations in terms of growth performance, negative effects on immune status were detected. The diet and fish immunity interactions at gut level have been widely discussed, although in vivo approaches have reported several limitations. In this sense, intestine explant culture system can be a valuable complementary tool to study the interactions between pathogenic bacteria and fish gut response, and the possible influence of environmental, breeding, rearing conditions or dietary components on the responsiveness of the innate immune system in fish.The object of this study was to test the impact of total substitution of fish meal by plant protein on the intestinal health of seabream (12g) in two growth stages: phase I (90 days), up to 68 g, and phase II (305 days), up to 250g. In phase II, the effects of the long term and short exposure (15 days) to plant protein diet were determined. In order to determine the effect of plant protein feeding on the innate immune response to bacterial pathogens, and an ex vivo procedure of intestine explants culture was implemented.ResultsFish showed less tolerance to dietary plant protein in phase I than in phase II, while the ex vivo assays indicated that the intestine from fish fed at short-term plant diets showed a higher immune response than at long term feeding.In relation to the immune response to bacterial challenge, a significant expression in pro-inflammatory cytokines IL-1β and IL-6 after 6 hours of exposure to V. algynoliticus, while COX-2 expression was significantly induced by P. damselae subsp. pisicida, showing positive high correlation between them.ConclusionsA differential health status was observed depending of growth stage, being stricter to the plant protein inclusion the younger fish. The new experimental system based on fish intestinal explants culture has been successfully implemented, becoming an effective methodology for ex vivo studies. Under ex vivo conditions, the bacterial challenge induced inflammatory and immune intestinal response, responding stronger those intestine of fish fed during a short-term with a total substitution of fish meal.

scholarly journals The Effect of Immunomodulatory Treatments on Anti-Dystrophin Immune Response After AAV Gene Therapy in Dystrophin Deficient mdx Mice

2021 ◽  
pp. 1-16
Author(s):  
Ning Li ◽  
Joanna E. Parkes ◽  
Rita Spathis ◽  
Melissa Morales ◽  
John Mcdonald ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
T Cell ◽  
Mdx Mice ◽  
Immunomodulatory Drugs ◽  
Strength Assessment ◽  
Gene Therapy Approach ◽  
The Impact

Background: AAV-based gene therapy is an attractive approach to treat Duchenne muscular dystrophy (DMD) patients. Although the long-term consequences of a gene therapy approach for DMD are unknown, there is evidence in both DMD patients and animal models that dystrophin replacement by gene therapy leads to an anti-dystrophin immune response that is likely to limit the long-term use of these therapeutic strategies. Objective: Our objective is to test whether the anti-dystrophin immune response is affected by immunomodulatory drugs in mdx mice after rAAV gene therapy. Methods: mdx mice were treated with rAAV microdystrophin alone or in combination with immunomodulatory drugs. Dystrophin expression in skeletal muscle was assessed by mass spectrometry. Immune responses were assessed by immunophenotyping, western blot for anti-dystrophin antibodies and flow cytometry assays for antigen-specific T-cell cytokine expression. The impact on muscle was measured by grip strength assessment, in vivo torque, optical imaging for inflammation and H&E staining of sections to assess muscle damage. Results: We found that AAV-9-microdystrophin gene therapy induced expression of microdystrophin, anti-dystrophin antibodies, and T-cell cytokine responses. Immunomodulatory treatments, rituximab and VBP-6 completely abrogated the anti-dystrophin antibody response. Prednisolone, CTLA4-Ig, and Eplerenone showed variable efficacy in blocking the anti-dystrophin immune response. In contrast, none of the drugs completely abrogated the antigen specific IFN-γ response. AAV-microdystrophin treatment significantly reduced inflammation in both forelimbs and hindlimbs, and the addition of prednisolone and VBP6 further reduced muscle inflammation. Treatment with immunomodulatory drugs, except eplerenone, enhanced the beneficial effects of AAV-microdystrophin therapy in terms of force generation. Conclusions: Our data suggest that AAV-microdystrophin treatment results in anti-dystrophin antibody and T-cell responses, and immunomodulatory treatments have variable efficacy on these responses.

scholarly journals Explaining the unexpected COVID-19 trends and potential impact across Africa.

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1177
Author(s):  
Daniel Oduro-Mensah ◽  
Ebenezer Oduro-Mensah ◽  
Peter Quashie ◽  
Gordon Awandare ◽  
Laud Okine
Keyword(s):  
Immune Response ◽  
Central Africa ◽  
Mortality Rates ◽  
Low Grade ◽  
Innate Immune Responses ◽  
Two Factors ◽  
The Impact ◽  
Low Grade Inflammation ◽  
Frequent Exposure

Official COVID-19 case counts and mortality rates across Africa are lower than had been anticipated. Research reports, however, indicate far higher exposure rates than the official counts in some countries. Particularly in Western and Central Africa, where mortality rates are disproportionately lower than the rest of the continent, this occurrence may be due to immune response adaptations resulting from (1) frequent exposure to certain pro-inflammatory pathogens, and (2) a prevalence of low-grade inflammation coupled with peculiar modifications to the immune response based on one’s immunobiography. We suggest that the two factors lead to a situation where post infection, there is a rapid ramp-up of innate immune responses, enough to induce effective defense and protection against plethora pathogens. Alongside current efforts at procuring and distributing vaccines, we draw attention to the need for work towards appreciating the impact of the apparently widespread, asymptomatic SARS-CoV-2 infections on Africa’s populations vis a vis systemic inflammation status and long-term consequences for public health.

Suppressed, but Not Forgotten

2011 ◽  
Vol 70 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Beat Meier ◽  
Anja König ◽  
Samuel Parak ◽  
Katharina Henke
Keyword(s):  
Memory Trace ◽  
Thought Suppression ◽  
Test Phase ◽  
Indirect Test ◽  
Final Test ◽  
Test Experiment ◽  
And Control ◽  
Cue Words ◽  
The Impact

This study investigates the impact of thought suppression over a 1-week interval. In two experiments with 80 university students each, we used the think/no-think paradigm in which participants initially learn a list of word pairs (cue-target associations). Then they were presented with some of the cue words again and should either respond with the target word or avoid thinking about it. In the final test phase, their memory for the initially learned cue-target pairs was tested. In Experiment 1, type of memory test was manipulated (i.e., direct vs. indirect). In Experiment 2, type of no-think instructions was manipulated (i.e., suppress vs. substitute). Overall, our results showed poorer memory for no-think and control items compared to think items across all experiments and conditions. Critically, however, more no-think than control items were remembered after the 1-week interval in the direct, but not in the indirect test (Experiment 1) and with thought suppression, but not thought substitution instructions (Experiment 2). We suggest that during thought suppression a brief reactivation of the learned association may lead to reconsolidation of the memory trace and hence to better retrieval of suppressed than control items in the long term.

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