Specific Host Immune Responses Research Articles

The immun function of dendritic cells in SFTS patients

ObjectivesSevere fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus in which host immune system suppression is thought to be crucial in disease development. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) critical for initiation and orchestration of the immune response. And it have been suggested that functionally impaired DCs may mediate the suppression of host-specific T-cell immune responses and thus facilitate viral persistence and disease progression.This study was designed to improve the in vitro culture method for DCs and investigate the different immunologic functions of DCs between SFTS patients and healthy people. MethodsAll confirmed SFTS patients (N = 10) were recruited from the Jinan Infectious Diseases Hospital in 2019; routine laboratory parameters were collected. The frequencies, phenotypes were analyzed by flow cytometry. And the levels of 8 cytokines in the cell culture supernatant were detected by flow cytometry. ResultsOn day 8 of the incubation period, cells were harvested and analyzed by flow cytometry. There were significant differences in the rates of CD1a-, CD83-positive cells between SFTS patients and healthy people (all P < 0.05). The detection of 8 cytokines in the culture supernatant showed that the expressions of IFN-α and IFN-γ in the culture supernatant of DC cells in SFTS patients were lower than those in normal people (P < 0.05, P < 0.01). ConclusionsThe present results indicate that DCs may be functionally impaired in SFTS. A decreased level of circulating mDCs was closely correlated with SFTS progression.

Can Erythropoietin Open a Novel Avenue for Periodontal Regeneration?

Periodontitis is a dramatic inflammatory disease, representing vigorous interactions between specific causative pathogens and host immune responses resulting in the activation of the destructive inflammatory cascade with the subsequent irreversible destruction of the teeth-supporting apparatus. This study aims to evaluate the effect of using erythropoietin (EPO) injectable hydrogel, as an additional therapeutic option to scaling and root planing (SRP) in the treatment of stage II periodontitis patients, and to assess its effect on the level of osteocalcin and interleukin (IL)-1β in the gingival crevicular fluid (GCF). A total number of 40 patients clinically diagnosed with stage II periodontitis were included. The participants were allocated into two equal groups: study and control groups. Patients in the control group received SRP, while those in the study group received SRP followed by injectable hydrogel containing EPO. Clinical parameters such as plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed at baseline and two months post treatment. GCF samples were collected at baseline and two months post treatment from both groups to analyze GCF IL-1β and osteocalcin levels using enzyme-linked immunosorbent assay (ELISA). Significant reductions in all tested clinical parameters were revealed in both groups in comparison to baseline values. A marked significant reduction in GCF IL-1β level was detected in the study group. However, two months post treatment, the osteocalcin level was decreased significantly in both groups. This preliminary study shows great promise for the local application of EPO hydrogel as an adjunct to SRP for the management of stage II periodontitis.

Virome Data Explorer: A web resource to longitudinally explore respiratory viral infections, their interactions with other pathogens and host transcriptomic changes in over 100 people.

Viral respiratory infections are an important public health concern due to their prevalence, transmissibility, and potential to cause serious disease. Disease severity is the product of several factors beyond the presence of the infectious agent, including specific host immune responses, host genetic makeup, and bacterial coinfections. To understand these interactions within natural infections, we designed a longitudinal cohort study actively surveilling respiratory viruses over the course of 19 months (2016 to 2018) in a diverse cohort in New York City. We integrated the molecular characterization of 800+ nasopharyngeal samples with clinical data from 104 participants. Transcriptomic data enabled the identification of respiratory pathogens in nasopharyngeal samples, the characterization of markers of immune response, the identification of signatures associated with symptom severity, individual viruses, and bacterial coinfections. Specific results include a rapid restoration of baseline conditions after infection, significant transcriptomic differences between symptomatic and asymptomatic infections, and qualitatively similar responses across different viruses. We created an interactive computational resource (Virome Data Explorer) to facilitate access to the data and visualization of analytical results.

Advances on adaptive immune responses affected by infectious bursal disease virus in chicken.

Infectious bursal disease (IBD) is an acute, highly infectious, and immunosuppressive disease caused by the infectious bursal disease virus (IBDV), which interferes with the immune system, causes hypoimmunity and seriously threatens the healthy development of the poultry industry. Adaptive immune response, an important defense line of host resistance to pathogen infection, is the host-specific immune response mainly mediated by T and B lymphocytes. As an important immunosuppressive pathogen in poultry, IBDV infection is closely related to the injury of the adaptive immune system. In this review, we focus on recent advances in adaptive immune response influenced by IBDV infection, especially the damage on immune organs, as well as the effect on humoral immune response and cellular immune response, hoping to provide a theoretical basis for further exploration of the molecular mechanism of immunosuppression induced by IBDV infection and the establishment of novel prevention and control measures for IBD.

ACE2 receptor polymorphism in humans and animals increases the risk of the emergence of SARS-CoV-2 variants during repeated intra- and inter-species host-switching of the virus.

Like other coronaviruses, SARS-CoV-2 has ability to spread through human-to-human transmission and to circulate from humans to animals and from animals to humans. A high frequency of SARS-CoV-2 mutations has been observed in the viruses isolated from both humans and animals, suggesting a genetic fitness under positive selection in both ecological niches. The most documented positive selection force driving SARS-CoV-2 mutations is the host-specific immune response. However, after electrostatic interactions with lipid rafts, the first contact between the virus and host proteins is the viral spike-cellular receptor binding. Therefore, it is likely that the first level of selection pressure impacting viral fitness relates to the virus's affinity for its receptor, the angiotensin I converting enzyme 2 (ACE2). Although sufficiently conserved in a huge number of species to support binding of the viral spike with enough affinity to initiate fusion, ACE2 is highly polymorphic both among species and within a species. Here, we provide evidence suggesting that when the viral spike-ACE2 receptor interaction is not optimal, due to host-switching, mutations can be selected to improve the affinity of the spike for the ACE2 expressed by the new host. Notably, SARS-CoV-2 is mutation-prone in the spike receptor binding domain (RBD), allowing a better fit for ACE2 orthologs in animals. It is possibly that this may also be true for rare human alleles of ACE2 when the virus is spreading to billions of people. In this study, we present evidence that human subjects expressing the rare E329G allele of ACE2 with higher allele frequencies in European populations exhibit a improved affinity for the SARS-CoV-2 spike N501Y variant of the virus. This may suggest that this viral N501Y variant emerged in the human population after SARS-CoV-2 had infected a human carrying the rare E329G allele of ACE2. In addition, this viral evolution could impact viral replication as well as the ability of the adaptive humoral response to control infection with RBD-specific neutralizing antibodies. In a shifting landscape, this ACE2-driven genetic drift of SARS-CoV-2 which we have named the 'boomerang effect', could complicate the challenge of preventing COVID with a SARS-CoV-2 spike-derived vaccine.

Lipidomic Analysis of Cervicovaginal Fluid for Elucidating Prognostic Biomarkers and Relevant Phospholipid and Sphingolipid Pathways in Preterm Birth

Cervicovaginal fluid (CVF) is an excellent specimen for monitoring preterm birth (PTB) as it characterizes cervical metabolites, the vaginal environment, and specific host immune responses. However, extensive lipid analysis of CVF to explain PTB has not been studied. In this study, we performed a systematic analysis combining high-throughput lipid analysis and omics to discover the unique metabolic properties of the cervix. Liquid chromatography-high resolution mass spectrometry successfully detected a total of 190 lipids in the CVF of 30 PTB and 30 term birth (TB) pregnant women. The whole lipidomics dataset analyzed by combining multivariate and univariate statistical analysis revealed 35 lipid biomarkers, including phospholipids and sphingolipids. Remarkably, sphingomyelin, which plays a physiologically essential role in sphingolipids, was significantly downregulated in PTB. Metabolic pathway study provides a close relationship between vaginal microbial organization and cell membrane formation, further supporting the robustness of our findings. Sphingolipids and phospholipids, which were determined to be important lipids for predicting PTB in our study, showed a high value of receiver operating characteristic (ROC) curve >0.7, indicating that a lipid diagnostic test and understanding the mechanism of lipids is highly related to the vaginal microbiome. Therefore, our result has high potential as a predictor of PTB.

Immune Response to Biofilm Growing Pulmonary Pseudomonas aeruginosa Infection.

Biofilm infections are tolerant to the host responses and recalcitrance to antibiotic drugs and disinfectants. The induced host-specific innate and adaptive immune responses by established biofilms are significantly implicated and contributes to the course of the infections. Essentially, the host response may be the single one factor impacting the outcome most, especially in cases where the biofilm is caused by low virulent opportunistic bacterial species. Due to the chronicity of biofilm infections, activation of the adaptive immune response mechanisms is frequently experienced, and instead of clearing the infection, the adaptive response adds to the pathogenesis. To a high degree, this has been reported for chronic Pseudomonas aeruginosa lung infections, where both a pronounced antibody response and a skewed Th1/Th2 balance has been related to a poorer outcome. In addition, detection of an adaptive immune response can be used as a significant indicator of a chronic P. aeruginosa lung infection and is included in the clinical definitions as such. Those issues are presented in the present review, along with a characterization of the airway structure in relation to immune responses towards P. aeruginosa pulmonary infections.

Leveraging Antibody, B Cell and Fc Receptor Interactions to Understand Heterogeneous Immune Responses in Tuberculosis

Despite over a century of research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), continues to kill 1.5 million people annually. Though less than 10% of infected individuals develop active disease, the specific host immune responses that lead to Mtb transmission and death, as well as those that are protective, are not yet fully defined. Recent immune correlative studies demonstrate that the spectrum of infection and disease is more heterogenous than has been classically defined. Moreover, emerging translational and animal model data attribute a diverse immune repertoire to TB outcomes. Thus, protective and detrimental immune responses to Mtb likely encompass a framework that is broader than T helper type 1 (Th1) immunity. Antibodies, Fc receptor interactions and B cells are underexplored host responses to Mtb. Poised at the interface of initial bacterial host interactions and in granulomatous lesions, antibodies and Fc receptors expressed on macrophages, neutrophils, dendritic cells, natural killer cells, T and B cells have the potential to influence local and systemic adaptive immune responses. Broadening the paradigm of protective immunity will offer new paths to improve diagnostics and vaccines to reduce the morbidity and mortality of TB.

Distinct lipid metabolic dysregulation in asymptomatic COVID-19

SummaryAsymptomatic infection is a big challenge in curbing the spread of COVID-19. However, its identification and pathogenesis elucidation remain issues. Here, by performing comprehensive lipidomic characterization of serum samples from 89 asymptomatic COVID-19 patients and 178 healthy controls, we screened out a panel of 15 key lipids that could accurately identify asymptomatic patients using a new ensemble learning model based on stacking strategy with a voting algorithm. This strategy provided a high accuracy of 96.0% with only 3.6% false positive rate and 4.8% false negative rate. More importantly, the unique lipid metabolic dysregulation was revealed, especially the enhanced synthesis of membrane phospholipids, altered sphingolipids homeostasis, and differential fatty acids metabolic pattern, implicating the specific host immune, inflammatory, and antiviral responses in asymptomatic COVID-19. This study provides a potential prediagnostic method for asymptomatic COVID-19 and molecular clues for the pathogenesis and therapy of this disease.

Genomic epidemiology of SARS-CoV-2 in the UAE reveals novel virus mutation, patterns of co-infection and tissue specific host immune response

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host–pathogen interaction investigation.

The Mucosal Innate Immune Responseto Cryptosporidium parvum, a Global One Health Issue.

Cryptosporidium parvum is an apicomplexan parasite that infects the intestinal epithelium of humans and livestock animals worldwide. Cryptosporidiosis is a leading cause of diarrheal-related deaths in young children and a major cause of economic loss in cattle operations. The disease is especially dangerous to infants and immunocompromised individuals, for which there is no effective treatment or vaccination. As human-to-human, animal-to-animal and animal-to-human transmission play a role in cryptosporidiosis disease ecology, a holistic ‘One Health’ approach is required for disease control. Upon infection, the host’s innate immune response restricts parasite growth and initiates the adaptive immune response, which is necessary for parasite clearance and recovery. The innate immune response involves a complex communicative interplay between epithelial and specialized innate immune cells. Traditional models have been used to study innate immune responses to C. parvum but cannot fully recapitulate natural host-pathogen interactions. Recent shifts to human and bovine organoid cultures are enabling deeper understanding of host-specific innate immunity response to infection. This review examines recent advances and highlights research gaps in our understanding of the host-specific innate immune response to C. parvum. Furthermore, we discuss evolving research models used in the field and potential developments on the horizon.

Leukocyte Activation Profile Assessed by Raman Spectroscopy Helps Diagnosing Infection and Sepsis.

Leukocytes are first responders to infection. Their activation state can reveal information about specific host immune response and identify dysregulation in sepsis. This study aims to use the Raman spectroscopic fingerprints of blood-derived leukocytes to differentiate inflammation, infection, and sepsis in hospitalized patients. Diagnostic sensitivity and specificity shall demonstrate the added value of the direct characterization of leukocyte's phenotype. Prospective nonrandomized, single-center, observational phase-II study (DRKS00006265). Jena University Hospital, Germany. Sixty-one hospitalized patients (19 with sterile inflammation, 23 with infection without organ dysfunction, 18 with sepsis according to Sepsis-3 definition). None (blood withdrawal). Individual peripheral blood leukocytes were characterized by Raman spectroscopy. Reference diagnostics included established clinical scores, blood count, and biomarkers (C-reactive protein, procalcitonin and interleukin-6). Binary classification models using Raman data were able to distinguish patients with infection from patients without infection, as well as sepsis patients from patients without sepsis, with accuracies achieved with established biomarkers. Compared with biomarker information alone, an increase of 10% (to 93%) accuracy for the detection of infection and an increase of 18% (to 92%) for detection of sepsis were reached by adding the Raman information. Leukocytes from sepsis patients showed different Raman spectral features in comparison to the patients with infection that point to the special immune phenotype of sepsis patients. Raman spectroscopy can extract information on leukocyte's activation state in a nondestructive, label-free manner to differentiate sterile inflammation, infection, and sepsis.

The respiratory microbiome after lung transplantation: Reflection or driver of respiratory disease?

With the introduction of high-throughput sequencing methods, our understanding of the human lower respiratory tract's inhabitants has expanded significantly in recent years. What is now termed the "lung microbiome" has been described for healthy patients, as well as people with chronic lung diseases and lung transplants. The lung microbiome of lung transplant recipients (LTRs) has proven to be unique compared with nontransplant patients, with characteristic findings associated with disease states, such as pneumonia, acute rejection, and graft failure. In this review, we summarize the current understanding of the lung microbiome in LTRs, not only focusing on bacteria but also highlighting key findings of the viral and the fungal community. Based on our knowledge of the lung microbiome in LTRs, we propose multiple opportunities for clinical use of the microbiome to improve outcomes in this population.

Identification of a novel proline-rich antimicrobial protein from the hemolymph of Antheraea mylitta.

Antimicrobial proteins (AMPs) are small, cationic proteins that exhibit activity against bacteria, viruses, parasites, fungi as well as boost host-specific innate immune responses. Insects produce these AMPs in the fat body and hemocytes, and release them into the hemolymph upon microbial infection. Hemolymph was collected from the bacterially immunized fifth instar larvae of tasar silkworm, Antheraea mylitta, and an AMP was purified by organic solvent extraction followed by size exclusion and reverse-phase high-pressure liquid chromatography. The purity of AMP was confirmed by thin-layer chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The molecular mass was determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry as 14 kDa, and hence designated as AmAMP14. Peptide mass fingerprinting of trypsin-digested AmAMP14 followed by de novo sequencing of one peptide fragment by tandem mass spectrometry analysis revealed the amino acid sequences as CTSPKQCLPPCK. No homology was found in the database search and indicates it as a novel AMP. The minimum inhibitory concentration of the purified AmAMP14 was determined against Escherichia coli, Staphylococcus aureus, and Candida albicans as 30, 60, and 30 µg/ml, respectively. Electron microscopic examination of the AmAMP14-treated cells revealed membrane damage and release of cytoplasmic contents. All these results suggest the production of a novel 14 kDa AMP in the hemolymph of A. mylitta to provide defense against microbial infection.

A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of −6.7 kcal/mol compared with the −6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.

Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic.

At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.

SARS-CoV-2 and Microbiological Diagnostic Dynamics in COVID-19 Pandemic

We have been introduced to "Coronavirus Disease 2019 (COVID-19)" disease with high mortality and transmission rate caused by a novel human coronavirus, in December 2019 and the microbiological diagnosis of the infection has been in the center of the focus to control the pandemic. It is necessary to understand the dynamics of the virus which was classified among the severe acute respiratory syndrome (SARS) related coronaviruses and named as SARS coronavirus 2 (SARS-CoV-2), to manage testing in the right strategy and for interpretation of the results. However, much remains unclear about the virus and the immune response. SARS-CoV-2, which is an enveloped, RNA virus has been shown to attach to the host cell receptor angiotensin converting enzyme 2 with spike (S) protein and membrane fusion is provided by transmembrane protease serine 2 (TMPRSS2) of the host cell. The most commonly used and reliable test for diagnosis of COVID-19 is reverse-transcribed polymerase chain reaction (RT-PCR) performed by using nasopharyngeal swabs or other respiratory tract specimens. Viral RNA is usually detected two three days before the onset of symptoms and in the first week from upper respiratory tract samples. If possible, the lower respiratory tract specimens are preferable in the second week, especially if former PCR is negative and pneumonia has developed. The clinical sensitivity of SARS-CoV-2 RNA tests has been reported around 55-75%. Negative RT-PCR test result does not exclude COVID-19 or SARSCoV-2 infection. It should also be noted that viral RNA positivity is not an evidence of active or infectious virus. SARS-CoV-2 infection can be also detected indirectly by testing the host specific immune response to the virus. There is an increasing interest in the use of SARS-CoV-2 antibody tests both for the diagnosis and public health surveillance. However, the antibody tests should not be used as the sole test for diagnosis and case management. Antibody tests are valuable tools in seroepidemiological studies. Anti-SARS-CoV-2 IgM, IgA and IgG antibodies have been shown to be detectable as early as 5th-14th days after the onset of symptoms and most of them become positive on the 21st day. False positivity has been reported more frequently with IgM and IgA tests due to low specificity. It was shown that clinical sensitivity of the diagnostic approach increases when RNA and total antibody tests were integrated as co-tests, especially after the second week of the disease. Specificity, sensitivity, positive and negative predictive values are needed to be evaluated with large and standard studies targeting populations with different prevalences. It is also necessary to create evidence with larger seroconversion studies. In this review article, the information and data obtained until today about SARS-CoV-2 and its microbiological diagnosis have been discussed.

Chemokine, cytokine and haematological profiles in Sprague-Dawley rats co-infected with Plasmodium berghei ANKA and Trichinella zimbabwensis-A laboratory animal model for malaria and tissue-dwelling nematodes co-infection

Malaria remains a major cause of mortality and morbidity in sub-Saharan Africa (SSA) and tissue-dwelling helminth parasites (TDHPs) are also prevalent in this region presenting a geographical overlap in endemicity. There is paucity of information on the specific host immune responses elicited at different phases of the life cycle by the co-infecting helminth parasites. This study aimed at using a laboratory animal model to determine selected chemokine, cytokine and hematological profiles in Sprague-Dawley rats co-infected with Plasmodium berghei ANKA (Pb) and a tissue-dwelling nematode, Trichinella zimbabwensis (Tz). One-hundred-and-sixty-eight male Sprague-Dawley rats (90–150g) were randomly divided into four experimental groups; Control (n = 42), Pb-infected (n = 42), Tz-infected (n = 42) and Pb + Tz-infected group (n = 42). Trichinella zimbabwensis infection (3 muscle larvae/g body weight per os) was done on day 0 while intra-peritoneal Pb infection (105 parasitised RBCs) was done at day 28 of the 42-day experimental study for the co-infection group which corresponded with day 0 of the Pb group on the protocol. Haematological parameters, cytokines (TNF-α, IL-10, IL-4, IL-6), chemokines (CXCL10, CCL5, CCL11) and burden of Tz adult worms and muscle larvae burden were determined as per need for each group. Results showed that Tz infection predisposed the co-infected animals towards rapid development of Pb parasitaemia during co-infection, reaching a higher peak percentage parasitaemia at day 7 post-infection than the Pb mono-infected group at day 6 post-infection. Animals in the co-infected group also exhibited severe anaemia, basophilia, neutrophilia, eosinophilia and lymphopenia at day 7 post Pb infection compared to the control groups. Significant elevation of Pb parasitaemia coincided with elevated pro-inflammatory cytokine TNF-α (P < 0.001), regulatory anti-inflammatory IL-10 (P < 0.001), and pro-inflammatory chemokines CXCL10 (P < 0.001) concentration in comparison to control group, at day 7 post Pb infection. Our results confirm that co-infection of Pb with Tz resulted in increased Pb parasitaemia compared to the control group in the early stages of infection and this might translate to severe malaria.

Current and Evolving Concepts on the Pathogenesis of Diverticular Disease.

Diverticulosis of the colon is the most common anatomic alteration of the human colon, and it is characterized by the out-pouching of the colonic mucosa and submucosa through the muscular layer. Recurrent abdominal pain is experienced by about 20% of patients with diverticulosis, and inflammation of diverticula may lead to acute diverticulitis. In the past few years, several studies have investigated the factors predisposing or triggering diverticular disease (DD) occurrence. Moreover, new physiopathological knowledge has been acquired. The aim of this study was to review current knowledge regarding the pathogenesis of DD. A search of PubMed and EMBASE database was performed to identify articles relevant to the pathogenesis of DD. Several papers have shown that genetic predisposition, environmental factors, and colonic dysmotility are implicated in the pathogenesis of DD. More recent studies have associated specific host immune responses, gut microbiota imbalance and therefore low-grade inflammation as contributors to symptom occurrence in DD and diverticulitis. Current and evolving evidence highlighted the role of genetic susceptibility, environment, colonic motility, visceral sensitivity, immune response, and microbiota in the pathogenesis of this disease. Further studies are required to identify potential targets for medical or surgical decision-making.

Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates

BackgroundSyphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens. MethodsTo test our hypothesis, we engineered non-infectious Borrelia burgdorferi strains to express the tp0897 (tprK) and tp0435 genes of Treponema pallidum subsp. pallidum and immunized two groups of rabbits by injecting recombinant strains intramuscularly with no adjuvant. TprK is a putative integral outer membrane protein of the syphilis agent, while tp0435 encodes the highly immunogenic T. pallidum 17-kDa lipoprotein, a periplasmic antigen that was also shown on the pathogen surface. Following development of a specific host immune response to these antigens as the result of immunization, animals were challenged by intradermal inoculation of T. pallidum. Cutaneous lesion development was monitored and treponemal burden within lesions were assessed by dark-field microscopy and RT-qPCR, in comparison to control rabbits. ResultsPartial protection was observed in rabbits immunized with B. burgdorferi expressing TprK while immunity to Tp0435 was not protective. Analysis of the humoral response to TprK antigen suggested reactivity to conformational epitopes. ConclusionsImmunization with native antigens might not be sufficient to obtain complete protection to infection. Nonetheless we showed that non-infectious B. burgdorferi can be an effective carrier to deliver and elicit a specific host response to T. pallidum antigens to assess the efficacy of syphilis vaccine candidates.