Iranian journal of immunology
Volume:18 Issue: 4, Autumn 2021

It was reported that targeting the Toll-like receptor9(TLR9) signaling pathway can be a promising therapeuticstrategy forinterventions in various inflammatory and infectiousdiseases. However,it was not known whether the human TLR9 isresponsive to Brucellacytidine-phosphate-guanosine (CpG) DNAsequences and activatesthehost’s innate immune system. The present study aimed to identify the novel humanTLR9agonists from Brucella CpG oligodeoxynucleotide(ODN) candidatesand verify their immune response regulatorymechanisms. Molecular docking methods were used to discover potentagonists of the human TLR9. The potential molecules were furthervalidated by Western blot and enzyme-linked immunosorbentassay(ELISA). The experiment results showed a strong interactionandgood compatibility between the human TLR9 and BrucellaODN-1molecule. In addition, the induction of immune response byBrucella ODN-1 is a CpG-specific response. Moreover, the effectsof Brucella ODN-1 on cytokine response are dependent on theTLR9-mediated NF-κB pathway. These results indicated that the Brucella ODN-1 molecule canserve as a starting point to discover or designmore potent and specific TLR9 agonists that have the potential usein the treatment of infectious diseases.

One of the main challenges in protein-based vaccines is the poor immunogenicity of antigens, which can be solved by the use of adjuvants. Advax is a novel microparticle polysaccharide adjuvant that in combination with antigens can induce both cellular and humoral immunity based on the intrinsic features of the antigen. It has been shown that poly(I:C) can be a suitable adjuvant for the PfMSP-142-based malaria vaccine. Advax is a suitable co-adjuvant for poly(I:C) to increase its half-life and reduce dose-dependent toxicity. To investigate whether advax alone or advax /poly(I:C) combination can enhance the immunogenicity with increased parasite inhibitory anti-PfMSP-142 antibodies in comparison to poly(I:C). Mice groups were inoculated with rPfMSP-142 alone or formulated in poly(I:C), poly(I:C)/advax, or advax. Then, humoral and cellular immune responses, the ratio of Th1/Th2 and growth inhibitory activity of induced antibodies were analyzed. Poly(I:C)/advax formulated PfMSP-142 induced higher levels of anti-PfMSP-142 IgG, IgG2a, and IgG2b antibodies relative to poly(I:C)-formulated PfMSP-142. The maximum ratio of IFN-γ/IL-4 (50.13) and gG2a/IgG1 (2.65), was induced in mice received advax-formulated PfMSP-142. Besides, poly(I:C)/advax formulated PfMSP-142 induced a higher ratio of IFN-γ/IL-4 (25.33) and IgG2a/IgG1 (1.89) when compared withpoly(I:C) alone. Strong growth inhibitory activity was observed inantibodies induced in mice receivedpoly(I:C)/advax-formulated PfMSP-142. These findings indicate that advax is a favorable adjuvant to be combined with poly(I:C), and this combination of adjuvants could induce Th1 immune responses and growthinhibitory antibodies against rPfMSP-142.

Pseudomonas aeruginosa is an important opportunistic pathogen, especially in patients with compromised host defense. To prepare the conjugate of detoxified lipopolysaccharide (D-LPS) and exotoxin A toxoid (T-ETA) from P. aeruginosa in gold nanoparticles (Au NPs) in a mice model. LPS and ETA were purified from P. aeruginosa PAO1. D-LPS was conjugated with T-ETA via the amidation method. Au NPs were bound to D-LPS-T-ETA conjugate via electrostatic interaction. Mice were immunized with D-LPS, D-LPS-Au NPs, T-ETA, T-ETA-Au NPs, D-LPS-T-ETA, D-LPS-T-ETA-Au NPs, D-LPS-Au NPs+T-ETA-Au NPs, Au NPs, and phosphate-buffered saline (PBS), and specific IgG titers were determined by the ELISA and the whole-cell ELISA methods. Mice in the vaccinated and control groups were exposed to a 2×LD50 of P. aeruginosa and mortality rates were recorded for one week. The results showed that vaccination by D-LPS, D-LPS-Au NPs, T-ETA, T-ETA-Au NPs, D-LPS-T-ETA, D-LPS-T-ETA-Au NPs and D-LPS-Au NPs+T-ETA-Au NPs induced specific IgG. Mice received the D-LPS-T-ETA-Au NPs conjugate showed significant protection against bacterial challenge. These data indicate that D-LPS-T-ETA-Au NPs conjugate has a significant immunogenicity potential to be applied as a new vaccine against Pseudomonas infections.

Echinococcosis is a common health problem in the Mediterranean and the Middle East. Many hydatid cysts remain asymptomatic, even in advanced age due to the slow growth of the parasite.

The present study aimed to investigate the oxidative and inflammatory responses in rats' echinococcosis induced by three different viability statuses of the Echinococcus granulosus (G6) as diagnostic markers.

Forty-eight male albino rats were injected intraperitoneally with three different viability statuses of the hydatid cyst fluid of the camel strain. The groups included: the negative control group (1), the low viable protoscoleces (2), the high viable protoscoleces fluid (3) not viable and not completely transformed to the calcareous status of protoscoleces fluid (4). Serum was harvested at the end of each week from the 9th to the 12th week post-infection for measuring the oxidative stress by total antioxidant capacity (TAC), and lipid peroxide (Malondialdehyde) (Malondialdehyde or MDA). . Splenic tissues from different groups werecollected for histopathological examination.

The results showed a histopathological change, a significantly decrease in TAC levels, and an increase in malondialdehyde, the TNF-α, and IL-10 levels of the infected groups compared with the uninfected group (P<0.05).

Our study conclude that the Echinococcosis induced severe oxidative stress and inflammatory responses including tissue necrosis and tissue degeneration the factors that can be used in the early stages of infection, avoiding hazards of contamination.

Interleukin-6 (IL-6) is a well-known proinflammatory cytokine with tumor promoting capacity in various forms of malignancies including breast cancer (BC). Data highlighted the substantial role of HPV in the pathogenesis of BC. Compelling evidence suggests the contribution of HPV in carcinogenesis through triggering inflammatory cytokines such as IL-6. Here, we assessed the correlation between the presence of HPV infection and the status of IL-6 expression and serum level in BC. 72 tissue specimens including tumoral (Case; n=36) and their adjacent normal tissues (Control; n=36) were used. Nested-PCR and Real-Time PCR were employed to identify HPV DNA and assess the expression of IL-6, respectively. In addition, 72 sera samples from BC patients (n=36) and an age-matched healthy control group (n=36) were taken to measure the IL-6 serum level by ELISA. Overall, the HPV DNA was detected in 19.4% (14/72) of samples. 33.33% (12/36) of cases and 5.5% (2/36) of the controls were found to be positive for HPV (P=0.003). The overexpression of IL-6 was observed in HPV+ samples compared to HPV- samples (P=0.05). However, the concentration of IL-6 serum level was remarkably different between patients and normal controls (P=0.0001). Intriguingly, IL-6 serum level was connected to the advanced clinical stage (III/IV), high grade (II/III), metastasis and, ER+ status of patients. Our finding indicated that the overexpression of the IL-6 may be connected to HPV infection in BC. Furthermore, the results reinforced the clinical significance and prognostic value of the serum IL-6 in BC patients.

According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19.

To determine the association of serum cytokine levels with COVID-19 severity.

We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico.

We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables.

Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.

Immune system has an important effect on pain-related disorders such as fibromyalgia syndrome (FMS). There is no specific laboratory technique for the diagnosis of FMS, but measuring serum proinflammatory cytokines may help. The purpose of our study was to determine the serum levels of immune mediators and their relationship with FMS symptoms. 25 healthy individuals and 29 FMS patients receiving pregabalin 150 mg/day for a minimum of 3 months were included in this study. FMS patients were diagnosed according to diagnostic criteria of the American College of Rheumatology (ACR 2010). Widespread pain index (WSI), fatigue, waking unrefreshed, cognitive symptoms, somatic symptoms, and Fibromyalgia Impact Questionnaire (FIQ) scores were evaluated in patients with FMS. Serum levels of proinflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IFN-γ, TNF-α) were assessed using enzyme-linked immunosorbent assay (ELISA). Proinflammatory cytokine levels were higher in the control group than patients with FMS (p <0.05). A positive correlation was found between age and WSI (P=0.037). In addition, a significant positive relationship was determined between IL-17 level and waking unrefreshed (P=0.049). There was no significant relationship between other cytokines and clinical findings. Lower proinflammatory cytokine levels identified in FMS patients may be related to pregabalin treatment, and there may be an impairment in the inflammatory response. On the contrary, IL-17 showed a positive correlation with waking unrefreshed.

Interleukin-37 (IL-37) is a recently described cytokine that emerges as a natural inhibitor of inflammatory and immune responses. However, IL-37 has not yet been investigated in bladder cancer, and its biological role is unknown.

The purpose of this study was to investigate IL-37 serum levels in patients with bladder cancer and determine whether they were linked to the patients' pathological characteristics.

IL-37 serum levels were measured using a commercial ELISA kit in 60 patients with transitional cell carcinoma (TCC) of the bladder (mean age: 64.55±12.93) and 50 healthy controls (mean age: 62.94±12.69). Non-parametric tests were used for statistical comparisons, and the Cohen's d effect size was calculated to evaluate the practical and clinical significance of the results.

Our findings indicated an increasing trend in IL-37 serum levels in patients with TCC (42.77±3.36 pg/ml) in comparison with controls (40.51±7.32 pg/ml, p=0.09). However, IL-37 serum levels were found to be significantly higher in male patients (44.72±3.81 pg/ml) and patients aged ≥70 (46.92±6.77 pg/ml) in comparison with male controls (29.96±3.30 pg/ml, p=0.026) and controls aged ≥70 (23.62±4.43 pg/ml, p=0.009). In comparison to similar controls, Cohen's d effect size for patients aged ≥70 years was found to be 0.90.

The findings reveal a higher serum level of IL-37 in patients with TCC, which might be clinically associated with immunosuppression and tumor growth. However, this is a preliminary study, and more research on the biological role of IL-37 and its potential therapeutic effects in bladder cancer is required.

Takayasu arteritis (TA) is a systemic vasculitis, affecting mainly the aorta and its branches.

To analyze the HLA class I and class II alleles in patients with TA and explore their relationship with clinical and demographic characteristics, and potential significance in prognosis.

Twenty-five, unrelated TA patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and the HLA-DQB1 loci. The frequencies of the HLA-A, HLA-B, and the HLA-DRB1 were compared with a control group of 1992, while the HLA-C and the HLA-DQB1 were compared with a group of 159 healthy, unrelated individuals.

Among TA patients, 5/25 (20%) were identified as the HLA-B*52 carriers. There was a significant difference in the HLA-B*52 allele frequency in the TA patients (10%) compared with the healthy controls (1.2%). Moreover, presence of the HLA-B*52 was associated with significantly earlier disease onset, more severe clinical presentations, and a poorer response to treatment. The HLA-C*03 was detected in 32% of patients and was present exclusively in those with a clinically mild form of the TA, indicating a putative protective effect.

These findings indicate that the HLA-B*52 allele contributes to a higher susceptibility to the TA whereas the HLA-C*03, can be a protective factor in the TA.