The impact of Haemophilus ducreyi cytolethal distending toxin on cells involved in immune response

2001 ◽  
Vol 30 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Liselott A. Svensson ◽  
Andrzej Tarkowski ◽  
Monica Thelestam ◽  
Teresa Lagergård

2003 ◽  
Vol 71 (12) ◽  
pp. 6971-6977 ◽  
Author(s):  
Leah E. Cole ◽  
Kristen L. Toffer ◽  
Robert A. Fulcher ◽  
Lani R. San Mateo ◽  
Paul E. Orndorff ◽  
...  

ABSTRACT Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. Neither naturally occurring chancroid nor experimental infection with H. ducreyi results in protective immunity. Likewise, a single inoculation of H. ducreyi does not protect pigs against subsequent infection. Accordingly, we used the swine model of chancroid infection to examine the impact of multiple inoculations on a host's immune response. After three successive inoculations with H. ducreyi, pigs developed a modestly protective immune response evidenced by the decreased recovery of viable bacteria from lesions. All lesions biopsied 2 days after the first and second inoculations contained viable H. ducreyi cells, yet only 55% of the lesions biopsied 2 days after the third inoculation did. Nearly 90% of the lesions biopsied 7 days after the first inoculation contained viable H. ducreyi cells, but this percentage dropped to only 16% after the third inoculation. Between the first and third inoculations, the average recovery of CFU from lesions decreased approximately 100-fold. The reduced recovery of bacteria corresponded directly with a fivefold increase in H. ducreyi-specific antibody titers and the emergence of bactericidal activity. These immune sera were protective when administered to naïve pigs prior to challenge with H. ducreyi. These data suggest that pigs mount an effective humoral immune response to H. ducreyi after multiple exposures to the organism.



Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.



Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.



2019 ◽  
Vol 25 (37) ◽  
pp. 4946-4967 ◽  
Author(s):  
Anna K. Kiss ◽  
Jakub P. Piwowarski

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products’ phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs’ bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs’ metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.



Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.



Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 33
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.



Author(s):  
Michael Halim

The Coronavirus pandemic has caused negative effects across the globe; mortality and morbidity being the main impact. After WHO, termed the disease a pandemic in March 2020, they gave in health guidelines to follow to control the spread of the disease. The health industry, academia, and different governments are united to develop and test various vaccines at an unprecedented speed to combat the pandemic fully and bring the world back to its feet. Some of the vaccines developed include Pfizer, Moderna, and AstraZeneca. However, just like other viruses, the SAR-CoV-2 virus keeps changing through mutation, as various variants, different from the first one are emerging. Evidence shows that the three new variants; UK, Brazil, and South Africa are more severe in terms of transmissibility, disease severity, evading of the immune response, and reducing the ability to neutralized antibodies, compared to the original coronavirus. With such knowledge of the existence of different strains, the arises concerns on whether the already available vaccines are effective enough in preventing the new COVID-19 strains. Studies are still underdeveloped to learn more on the virologic, epidemiologic, and clinical characteristics of the ever-emerging variants. This research, through a systemic review of literature, seeks to find out whether the variants of SAR-CoV-2 have an impact on the efficacy of various vaccines developed in fighting the disease and the entire body’s immune response.



2021 ◽  
Vol 28 ◽  
Author(s):  
Douglas Henrique Pereira Damasceno ◽  
Arthur Aguiar Amaral ◽  
Cecília Andrade Silva ◽  
Ana Cristina Simões e Silva

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.



Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3198 ◽  
Author(s):  
Francesco Pecora ◽  
Federica Persico ◽  
Alberto Argentiero ◽  
Cosimo Neglia ◽  
Susanna Esposito

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).



Author(s):  
Loris Zamal ◽  
Marco Rocchi

The present work analyses in detail the published data on ChAdOx1 nCoV-19 vaccine and provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as the regimen of homologous vaccination with ChAdOx1 nCoV-19 vaccine is applied and interferes with efficacy of the vaccine when the interval between prime and boost doses is less than three months. Second, longitudinal studies suggest that ChAdOx1 nCoV-19 vaccine provides sub-optimal efficacy against UK variant of SARS-CoV-2, which appears to have an increased transmissibility over the ancestral SARS-CoV-2 among vaccinated people. At the moment, ChAdOx1 nCoV-19 vaccine is able to reduce the severity of symptoms and transmissibility; however, if the vaccinated individuals do not maintain everyday preventive actions, they could turn into potential spreaders, thus accelerating the process of generation of new viral variants due to the selective pressure of immune response. Prediction and possible consequences of the SARS-CoV-2 evolution and repeated anti-SARS-CoV-2 vaccinations are discussed. Since the impact of emerging SARS-CoV-2 variants suggests that vaccines are unlikely to be effective in quickly solving the pandemic crisis, it is highlighted the need to keep searching for new and more efficacious pharmacotherapy for COVID-19, such as those targeting ACE2 and ADAM17 zinc-metalloprotease activities.



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