Moderate Immune Response Research Articles

In vivo analysis of a proprietary glass-based adhesive for sternal fixation and stabilization using rabbit and sheep models

Wire cerclage remains the standard method of care for sternal fixation, following median sternotomy, despite being beset with complications. An emerging treatment option has been to augment the wires with an adhesive. A patented ionomeric glass (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) has been used to formulate GPC+, a glass polyalkenoate cement (GPC), by mixing it with poly(acrylic) acid (PAA) and de-ionized water. In a human cadaver study, this material, when applied with wire cerclage, was able to significantly reduce sternal instability. However, the material has yet to be tested in pertinent animal models. Here, after a series of physical and mechanical tests to confirm suitability of the experimental material for implantation, three samples of GPC+ were implanted in either the tibia or femur of three different rabbits, alongside sham defects, for two different time modalities. A further seven samples of GPC+ and one poly(methyl methacrylate) control (PMMA) were implanted in either the tibia or femur of two different sheep. The sheep containing the PMMA was sacrificed at 8 weeks and the other at 16 weeks, to evaluate time dependent biological response. Upon sacrifice, microCT images were acquired and histology slides prepared for analysis. All three GPC+ samples implanted in the rabbit model, for the two time modalities, were characterized by minimal bone resorption along with a mild inflammatory response. Five of the seven GPC+ materials implanted in the sheep model (all three implanted for 8 weeks and two of those implanted for 16 weeks) were associated with mild to moderate immune response, comparable to that observed with PMMA, as well as mild bone resorption. The remaining two GPC + materials (implanted in the sheep model for 16 weeks) exhibited no bone resorption or inflammatory response and appeared to stimulate increased bone density at the implant site. These results suggest that GPC + can be a viable bone adhesive for use in hard tissue applications such as sternal fixation and stabilization.Experiments performed to synthesize & test Sr-doped glass adhesive for sternal fixation. (1) Sr-doped ionomeric glass fired, ground down and mixed with aqueous polyacrylic acid to produce the adhesive. (2) Adhesive characterized and tested by a suite of laboratory-based tests to ensure suitability for implantation. (3) Adhesive implanted into a rabbit model (distal femur, 12 weeks post implantation) where micro-CT images confirmed an excellent bone/cement interface, no evidence of bone resorption and some bone remodelling. (4) Adhesive subsequently implanted into a sheep model; at 16-weeks, a continuous bone—adhesive interface is seen suggesting no bone resorption. There was an increase in the peri-implant radiodensity, suggesting enhanced mineral content of the bone surrounding the GPC+ implant.

SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies.

So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.

Immune Function Testing and Long-Term Immune-Related Outcomes among Heart Transplant Recipients

<h3>Purpose</h3> The Cylex ImmuKnow (IK) assay, a rapid quantitative assessment of T-cell-mediated function, is used to monitor immunosuppression among heart transplant (HT) recipients. It is unclear whether the IK assay can aid in characterizing the long-term risk of adverse immune-related events among HT recipients. <h3>Methods</h3> We conducted a single-center, retrospective, cohort study of all single organ HT recipients from 2014 to 2018. The IK assay divided subjects into low, moderate, or high immune response categories at 6-month, 1-, and 2-year intervals. IK assay categorization was correlated to the primary composite outcome which included acute cellular rejection, antibody-mediated rejection, development of donor-specific antibodies, coronary allograft vasculopathy, and death over 2 years of follow-up. <h3>Results</h3> 134 single organ HT recipients were included (median age 56.5 years, 70% male). On an immunosuppressive regimen of tacrolimus, prednisone, and mycophenolate mofetil, most subjects had low and moderate immune response levels at 6 months (53% low vs 37% moderate vs 10% high). A higher proportion of subjects exhibited moderate immune response at 1 (44% low vs 47% moderate vs 9% high) and 2 years (29% vs 60% vs 11%). The composite outcome occurred in 14% of subjects by 6 months, 35% by 1 year, and 36% by 2 years. There was no difference in the rate of the composite outcome or its individual components between the immune response groups at any of the time points (Fig. 1B). The relative change in an individual's IK score between timepoints was not associated with the composite outcome. <h3>Conclusion</h3> On standard immunosuppression, a majority of HT recipients exhibit low to moderate immune response per the IK assay. The IK assay reflects expected increases in immune function with reduced immunosuppression. IK assay-based immune response categorization does not appear to aid in identifying HT recipients at risk for adverse immune-related events in the long-term. The results are limited by the sample size and low event rates.

An iTRAQ-based comparative proteomic analysis of grass carp infected with virulent and avirulent isolates of grass carp reovirus genotype II

Genotype II of grass carp reovirus (GCRV) is an epidemic strain that is devastating to the grass carp industry in China. Infections of grass carp caused with virulent GCRV-HuNan1307 and avirulent GCRV-GD1108 isolates were carried out to determine the underlying pathogenic mechanisms. The differential host protein response was examined after infection with both virus isolates using an iTRAQ-based comparative quantitative proteomics. Differentially expressed proteins for GD1108 (34) and HuNan1307 (222) infections were identified and determined canonical pathways and functional networks involved in both GCRV infections. Infection with HuNan1307 activated the RIG-I pathway leading to antiviral response as well as the Jak-STAT pathway that governs general metabolic functions. These pathways were not activated by infection with the avirulent isolate. Infection with HuNan1307 also induced an abbreviated an intense immune response and lead to major disorders of the metabolism. In contrast, the GD1108 infection induced a mild and moderate immune response leaving basic metabolism unchanged. This study provides a comprehensive view at the protein level of the underlying pathogenic mechanisms used by a virulent GCRV type II isolate. SignificanceGenotype II of grass carp reovirus (GCRV) is an epidemic strain that is devastating to the grass carp industry in China. The unclear etiological characters, genetic variation and pathogenesis of GCRV genotype II blocked the development of techniques as well as products on prevention and control of grass carp haemorrhagic disease (GCHD). Here, iTRAQ strategy was firstly used to compare the proteomes of grass carp infected with virulent and avirulent isolates of GCRV genotype II. The obtained data showed that abbreviated and intense immune response and disorders of the metabolism were reasons for the mortality of fish infected with virulent GCRV isolate. The results would provide a train of thought to promote the development of techniques as well as products on prevention and control of GCHD.

Synthesis and immunogenicity of Brucella monovalent neoglycoconjugate

Brucellosis is a highly infectious zoonotic disease caused by Brucella. It is necessary to control and eliminate brucellosis. The cell wall O-polysaccharides of pathogenic Brucella species are homopolymers of the rare sugar 4,6-dideoxy-4-formamido-α-d-mannopyranose. Herein, one neoglycoconjugate was successfully synthesized based on disaccharide [Rha4NFo(1 → 2)Rha4NFo] as epitope. Disaccharide specific antibodies were detected by ELISA and the immune protective effect was further evaluated with PBS as control. The result showed that the synthetic neoglycoconjugate can produce moderate immune responses in mice and significantly decreased splenic Brucella M5 burden comparing with control group. The chemically defined antigen identified the A antigenic determinant and provided a structural basis for understanding the fine specificity of polyclonal antibodies that bind the A antigen. The neoglycoconjugate shows the potential in detection reagent or vaccine development for brucellosis.

Chemo-enzymatic synthesis of the ALG1-CDG biomarker and evaluation of its immunogenicity

Congenital disorders of glycosylation (CDG) are a growing group diseases that result from defects in genes involved in glycan biosynthesis pathways. One tetrasaccharide, i.e., Neu5Ac-α2, 6-Gal-β1, 4-GlcNAc-β1, 4-GlcNAc, was recently reported as the biomarker of ALG1-CDG, the disease caused by ALG1 deficiency. To develop a novel diagnostic method for ALG1-CDG, chemo-enzymatic synthesis of the tetrasaccharide biomarker linked to phytanyl phosphate and the biomarker’s immune stimulation were investigated in this study. The immunization study using liposomes bearing phytanyl-linked tetrasaccharide revealed that they stimulated a moderate immune response. The induced antibody showed strong binding specificity for the ALG1-CDG biomarker, indicating its potential in medical applications.

Effect of Imiquimod on Tachyzoites of Toxoplasma gondii and Infected Macrophages in vitro and in BALB/c Mice.

Treatment for toxoplasmosis is not completely successful because of their unwanted side effects, and new treatments are needed. Imiquimod has ability to moderate immune response and used to treat a wide variety of infections and tumors. The aim of the present study was to evaluate the effect of imiquimod on the tachyzoites of T. gondii and infected macrophages in vitro and in BALB/c mice. The viability of T. gondii was assessed in the presence of various concentrations of imiquimod by direct counting after 6 and 24 h. The MTT assay was used to identify the viability of uninfected macrophages. The apoptotic effects were determined with flow cytometry on the tachyzoites and infected macrophages. For evaluation of parasite load in pre-treatment or post-treatment of macrophages Quantitative real time PCR (qPCR) was performed. For in vivo experiments, BALB/c mice received imiquimod before and after challenge with parasites. The mortality rate of mice, parasite numbers in spleen, and the INF-γ and IL-4 cytokine levels in spleen lymphocytes were evaluated. Imiquimod demonstrated anti-Toxoplasma effects by reducing the number of tachyzoites. The results of flow cytometry for drug-treated tachyzoites showed that apoptosis did not rise significantly relative to the control group (p < 0.05). Moreover, apoptosis was enhanced in infected macrophages as the concentration of imiquimod was reduced. The parasitic burden in imiquimod pretreated macrophages was significantly lower than those treated after infection (p < 0.01). A marked reduction was observed in survival rate, parasite load and INF-γ level in BALB/c mice that received imiquimod before parasitic challenge relative to those received drug after parasitic challenge (p < 0.01). Overall, imiquimod in the pretreated group had greater anti-Toxoplasma effects than imiquimod in posttreated group in vitro and in vivo. imiquimod may be considered as a candidate for use against Toxoplasmosis both therapeutically and prophylactically.

Clinicopathological Analysis and Prognostic Assessment of Transcobalamin I (TCN1) in Patients with Colorectal Tumors.

BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide. Overall survival (OS) of patients is largely dependent on disease stage at diagnosis and/or surgical resection. TCN1 mainly encodes the vitamin B12 transporter, transcobalamin. Early studies show that TCN1 is a marker of CRC progression, but the impact of TCN1 on survival is unclear.Material/MethodsWe reviewed and analyzed colorectal tumor records, summarized the clinicopathological data, performed immunohistochemical detection of TCN1 again, and semi-quantitatively analyzed protein expression in tumor tissue, non-tumor tissue, and lymph nodes. We followed up patients for 5-year survival.ResultsOf 123 patients, 60 (48.7%) had a strong TCN1 immunohistochemical reaction, 36 (29.3%) had a moderate immune response, and 27 (22.0%) had weak expression. The level of immunohistochemical reactivity of TCN1 was correlated with the degree of histological differentiation (H (2.92)=4.976; P=0.083). Survival analysis showed that OS in patients with low TCN1 expression was significantly longer than that in the medium and high TCN1 expression groups (P=0.045). Five-year OS in patients with low, medium, and high TCN1 expression was 88.9%, 50.0%, and 40.0%, respectively. In univariate analysis, TCN1 immune expression was significantly correlated with the 5-year survival rate.ConclusionsAlthough independent risk factors affecting survival of patients with CRC are age, serum CA125, CA19-9, lymph node metastasis, and nerve invasion, negative factors affecting overall 5-year survival in TCN1 should not be ignored, because its high expression suggests a worse clinical prognosis.

Immune Function Testing and Donor-Specific Antibody Production among Heart Transplant Patients

De novo donor-specific antibody (DSA) production has been correlated to the development of antibody-mediated rejection after heart transplantation. It is unclear whether the Cylex ImmuKnow (IK) assay - a rapid, quantitative assessment of T-cell-mediated immune function designed to monitor immunosuppression response - can be a useful tool in overall immunosuppression and identification of patients at risk for de novo DSA production. We hypothesize that, among heart transplant recipients, increased immune function activity as measured by the IK assay would correlate with de novo DSA production. We conducted a single center cohort study including all consecutive single organ heart transplant recipients from 2014 to 2018. The IK assay categorized subjects into low, moderate, or high immune response levels at 6, 12, and 24-month intervals. De novo DSA production based on human leukocyte antigen antibody testing was correlated to IK immune response levels at these time points. 122 single organ heart transplant recipients were included. High immune response levels were noted in 10%, 9%, and 12% of subjects at 6, 12, and 24-months, respectively. Compared to baseline, de novo DSA production was noted in 21%, 23%, and 25% of subjects at the respective time intervals. 6-month IK category did not correlate with DSA production at 6 (r = -0.03, p=0.9), 12 (r = -0.03, p=0.9), or 24 months (r = 0.15, p=0.3). Similar findings were noted at 12 and 24 months. Being in a high IK category at any interval was not associated with de novo DSA production at any time point (p>0.05). Univariate analysis of demographic factors, induction agents used, and co-morbidities (including EMV or CBV infection status) did not reveal significant associations with de novo DSA production. High T-cell-mediated immune response levels, a possible indicator of under-suppression, as measured by the IK assay were not associated with de novo DSA production after heart transplantation.

A role of peptidoglycan recognition proteins in regulating innate immune response

By now, a whole number of pathogenic antibiotic-resistant or tolerant microorganisms has been progressively increased. Hence, efficient fight against them requires to change the class of antibiotics, increase their dose, or develop new antimicrobial drugs. On the contrary, another option could rely on augmenting innate immunity. During coevolution, eukaryotes have developed several ways for their protection against microorganisms. Innate immunity conserved in all multicellular organisms. The essential principles of innate immunity include recognition of a foreign structures and their subsequent destruction. A set of specific receptors recognize conserved pathogen-derived structures. Elimination occurs due to phagocytosis and cleavage, e.g. via oxidative burst in phagocytic cells, compliment system or antimicrobial peptides. Recognition system in innate immunity is based on the pattern recognition receptors. Due to the pathogen diversity, multiple conserved structures typical to pathogens (e.g. lipopolysaccharide, peptidoglycan, flagellin etc.) are sensed by numerous receptors. The family of peptidoglycan recognition proteins is among such receptors, which were first isolated in 1996 from the silkworm Bombyx mori and mice. Later, it was demonstrated that this family is conserved and its members are found in insects, fish and mammals. Here, functions of insect peptidoglycan recognition proteins in Drosophila melanogaster as well as mammals are discussed. Such proteins are expressed mainly in liver cells (insects — in adipose tissue cells as analogue of mammalian liver), intestinal cells, and epidermis. Numerous studies demonstrate that peptidoglycan-recognition proteins moderate immune response, and may act as antimicrobial proteins, or to regulate microbiota as well as prevent enterocyte activation and restrict inflammatory response. Due to evolutionary conservatism observed for such proteins and inability for bacteria to evade their protective effects, it seems promising to use peptidoglycan recognition proteins in a combination therapeutic approach against antibiotic-resistant and antibiotic-tolerant forms of microorganisms.

Natural and Induced Tolerogenic Dendritic Cells.

Dendritic cells (DCs) are highly susceptible to extrinsic signals that modify the functions of these crucial APCs. Maturation of DCs induced by diverse proinflammatory conditions promotes immune responses, but certain signals also induce tolerogenic functions in DCs. These "induced tolerogenic DCs" help to moderate immune responses such as those to commensals present at specific anatomical locations. However, also under steady-state conditions, some DCs are characterized by inherent tolerogenic properties. The immunomodulatory mechanisms constitutively present in such "natural tolerogenic DCs" help to promote tolerance to peripheral Ags. By extending tolerance initially established in the thymus, these functions of DCs help to regulate autoimmune and other immune responses. In this review we will discuss the mechanisms and functions of natural and induced tolerogenic DCs and offer further insight into how their possible manipulations may ultimately lead to more precise treatments for various immune-mediated conditions and diseases.

Role of immune nutrients in the nutritional support treatment

Immune nutrient is one of the hotspots of surgical nutrition therapy in recent years, and its clinical application in critically ill patients during the perioperative period is particularly drawing attention. Omega-3 polyunsaturated fatty acids, glutamine, arginine, dietary fiber and other immune nutrients can coordinate inflammatory response of the body, maintain a moderate immune response, protect the integrity of intestinal mucosal barrier function, and reduce bacterial translocation. However, there are some controversies in the effects of various immune nutrients on the prognosis of patients between clinical research results. Key words: Critical illness; Immune nutrient; Nutritional support; Omega-3 polyunsaturated fatty acids; Glutamine; Arginine

Expression Kinetics and Innate Immune Response after Electroporation and LNP-Mediated Delivery of a Self-Amplifying mRNA in the Skin

In this work, we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation and lipid-nanoparticle (LNP)-mediated delivery in the skin of mice. Intradermal electroporation of the sa-RNA resulted in a plateau-shaped expression, with the plateau between day 3 and day 10. The overall protein expression of sa-RNA was significantly higher than that obtained after electroporation of plasmid DNA (pDNA) or non-replication mRNAs. Moreover, using IFN-β reporter mice, we elucidated that intradermal electroporation of sa-RNA induced a short-lived moderate innate immune response, which did not affect the expression of the sa-RNA. A completely different expression profile and innate immune response were observed when LNPs were used. The expression peaked 24 h after intradermal injection of sa-RNA-LNPs and subsequently showed a sharp drop. This drop might be explained by a translational blockage caused by the strong innate immune response that we observed in IFN-β reporter mice shortly (4 h) after intradermal injection of sa-RNA-LNPs. A final interesting observation was the capacity of sa-RNA-LNPs to transfect the draining lymph nodes after intradermal injection.

The Tsetse Fly Displays an Attenuated Immune Response to Its Secondary Symbiont, Sodalis glossinidius.

Sodalis glossinidius, a vertically transmitted facultative symbiont of the tsetse fly, is a bacterium in the early/intermediate state of its transition toward symbiosis, representing an important model for investigating how the insect host immune defense response is regulated to allow endosymbionts to establish a chronic infection within their hosts without being eliminated. In this study, we report on the establishment of a tsetse fly line devoid of S. glossinidius only, allowing us to experimentally investigate (i) the complex immunological interactions between a single bacterial species and its host, (ii) how the symbiont population is kept under control, and (iii) the impact of the symbiont on the vector competence of the tsetse fly to transmit the sleeping sickness parasite. Comparative transcriptome analysis showed no difference in the expression of genes involved in innate immune processes between symbiont-harboring (GmmSod+) and S. glossinidius-free (GmmSod–) flies. Re-exposure of (GmmSod–) flies to the endosymbiotic bacterium resulted in a moderate immune response, whereas exposure to pathogenic E. coli or to a close non-insect associated relative of S. glossinidius, i.e., S. praecaptivus, resulted in full immune activation. We also showed that S. glossinidius densities are not affected by experimental activation or suppression of the host immune system, indicating that S. glossinidius is resistant to mounted immune attacks and that the host immune system does not play a major role in controlling S. glossinidius proliferation. Finally, we demonstrate that the absence or presence of S. glossinidius in the tsetse fly does not alter its capacity to mount an immune response to pathogens nor does it affect the fly’s susceptibility toward trypanosome infection.

Icelandic ovine Mycoplasma ovipneumoniae are variable bacteria that induce limited immune responses in vitro and in vivo.

Mycoplasma ovipneumoniae is a pathogen that causes atypical pneumoniae in sheep and goats. While infection of lambs can induce strong immune responses, typically measured as serum antibodies, experimental vaccines appear to induce lower antibody titres. The purpose of this study was to better understand the bacterium and its interaction with the host, in order to improve the vaccination strategy. We designed primers to compare seven M. ovipneumoniae gene sequences, in addition to the 16S sequence typically used, to estimate the variability between isolates. In addition, we labelled bacteria with a two-step process to examine whether bacteria could be intracellular as well as on the host surface in vitro. Finally, we vaccinated sheep four times and examined the induction of humoral and cellular responses. We were able to reliably amplify the seven housekeeping gene sequences to examine variability of the different isolates, and the bacteria could be found intracellularly, as well as on the host cell surface. Four vaccinations of sheep produced only modest humoral and cellular responses in this study, likely due to previous exposure of the animals to mycoplasmas. The moderate immune responses seen in this study indicate that previous exposure to mycoplasmas is a challenge for vaccination of lambs against M. ovipneumoniae. However, an alternative vaccination strategy, e.g. utilizing a recombinant vaccine, may overcome this vaccination hurdle in endemic regions and we suggest a possible vaccine candidate.

Prevention of Dermal Abscess Formation Caused by Staphylococcus aureus Using Phage JD007 in Nude Mice.

Aim: In this study, Staphylococcus phage JD007 bactericidal activity and induced immune responses during treatment were assessed in a dermal abscess model.Materials and Methods: Dermal abscesses in nude mice were established by injecting a clinical isolate of S. aureus SA325 isolated from the back under-dermal abscess of an in-patient.Results: Phage JD007 was able to inhibit the growth of S. aureus SA325 at MOI = 1 or 10, significantly preventing the formation of dermal abscesses. Moderate immune responses were observed in the prevention group through detection of cytokines.Conclusion: Phage JD007 inhibits the formation of dermal abscesses caused by a clinical S. aureus strain in nude mice without robust immune responses.

Aged Mice are More Resistant to Influenza Virus Infection due to Reduced Inflammation and Lung Pathology.

Immune responses are a double-edged sword. Effective and appropriate immune responses capable of controlling viral infection while also largely preserving tissue integrity, are critical for host survival. Too strong immune responses might result in immune pathology, while too weak immune responses might cause viral persistence. Physiologic ageing is accompanied with a decline in the normal functioning of the immune system, which is termed as "immunosenescence". We show that aged mice (16-19 months old) are more resistant to influenza A virus (IAV) infection than the young mice. Strong immune responses in the young mice after IAV infection result in faster clearance of virus, but also cause severe lung injury and higher mortality rate. While in the aged mice, the delayed and milder immune responses contribute to reduced pulmonary damage, and are still capable to clear the infection even with a slower kinetics, displaying a more resistant phenotype during IAV infection. Hence, our work demonstrates that moderate immune responses as a decline with ageing in the aged mice balance the immune pathology and viral clearance, might be beneficial for the host during certain circumstances. Our results provide important insight to our basic knowledge of immunosenescence and immune defenses to invading pathogens. Further, our results indicate that age factors should be considered when investigating the vaccination and therapeutic strategies for severe IAV infection.

Endolysosomal protease susceptibility of Amb a 1 as a determinant of allergenicity

summary In the absence of extrinsic adjuvants, purified Amb a 1 induced a strong Th2-polarized immune response in mice. This high allergenic activity seems to be linked to the allergen’s susceptibility to endolysosomal proteolysis.

Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin.

As one of the pathogen-associated molecular patterns (PAMPs), flagellin is recently utilized as a potent adjuvant for many subunit vaccines. In this study, a truncated flagellin (tFL) with deletion of the hypervariable regions was adopted as a carrier-adjuvant by chemical conjugation with a chimeric malaria antigen M.RCAg-1 (M312) via a heterobifunctional polyethylene glycol (PEG) linker. After booster immunization in mice without any extra adjuvants, the M312-PEG-tFL conjugates elicited M312-specific antibody titers 100-1000 times higher than M312 and 10-100 times higher than the physical mixture of M312 and tFL. The elicited specific antibodies could recognize the native parasites, and the immunofluorescence assay (IFA) titer was 2100 for M312-P5k-tFL, which was about 7 times higher than M312. Furthermore, the IFA titers of the conjugates were comparable to the positive control of complete Freund's adjuvant (CFA). Compared to M312, the M312-PEG-tFL conjugates enhanced the proliferation index, lymphocyte activation, and memory T-cell generation. IgG subclasses of sera and cytokines analysis of splenocytes showed that conjugation with tFL could slightly trigger the Th1 polarization, while the antigen alone predominantly induced a Th2-biased immune response. Furthermore, a more-efficient innate immune response was provoked by the M312-PEG-tFL conjugates, as determined by the detection of antigen-specific TNF-α secretion by splenocytes. Our results indicated that tFL mainly retained the function as an agonist of TLR5. Conjugation of antigen to tFL could induce strong humoral and moderate cellular immune responses. Thus, conjugation of antigen to tFL as a potent carrier-adjuvant is an effective strategy for developing a promising protein-based vaccine.

Regulatory function of parasites in autoimmune disease – outcome from experimental model infection

It is estimated that more than half of the nowadays known species are pathogenic parasites. Among macroparasites gastrointestinal nematodes are one of most common and having significant impact on life and health. Those organisms reveal strong, specific immune response in host, involving primary mechanisms associated with regulatory and Th2 cells. Referring to immunomodulatory abilities of helminths, parasite infections started to be considered as a possible therapy for many autoimmune diseases. Clinical trials on 2nd and 3rd stage are conducted in spite that treatment has not been recognized as safe for common use. Despite that the safety of treatment with parasites is still controversial and widely discussed. Our knowledge about mechanisms used by helminth to moderate immune response is still inadequate to predict possible effect of long lasting parasite infection on individual patients.