Attenuation of inflammatory response in the EAE model by PEGlated nanoliposome of pistachio oils.

The aim of this study was to investigate the effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) to attenuate the inflammatory response in the EAE model by modulating of NFKB and oxidative stress signaling pathway. Real-time PCR demonstrated that the administration of 10%v/v PEGNLPUOs significantly decreased the expression level of AKT1, MAPK, and NFKB genes from NFKB signaling pathway and MGST1, NOS2, and HO-1 genes from oxidative stress signaling pathway. This study showed that the administration of pistachio oil and PEGNLPUOs at a concentration of 10%v/v decreased the number and percentage of Th1(CD4+) and increased Th2(CD8+) cells.

IL-17A and IL-23: plausible risk factors to induce age-associated inflammation in Alzheimer's disease.

Background: Aging and its complications such as Alzheimer's disease (AD) are associated with chronic low-grade inflammation entitled age-associated inflammation. However, the main mechanisms whichinduce age-associated inflammation in aging and AD are yet to beclarified. L-23/IL-17A axis plays important roles in the induction of inflammation and consequently autoimmune disease. This review evaluates the main roles played by IL-17A, IL-23, and IL-17A/IL-23 axis in the pathogenesis of age-associated inflammation in AD patients. Result: IL-23/IL-17A axis, is an important factor participate in the pathogenesis of age-associated inflammation. The genetic variations and microbial infection can be considered as the most important candidates to induce AD via upregulation of IL-17A. IL-17A also deteriorates AD via induction by amyloid-ß. IL-17A participates in the induction of AD by increasing neutrophils infiltration to brain, induction of neuroinflammation, increase in FASL, and amyloid-ßdeposition as well as activation of microglia. Conclusions: Due to the important roles played by IL-23/IL-17A axis in AD pathogenesis, it can be considered as a target for immunotherapy against AD. Abbreviations: Aß: ß-Amyloid; AD: Alzheimer's disease; CD: cluster of differentiation; DAMPs: Damage-associated molecular patterns; DCs: dendritic cells; HLA: human leukocyte antigen; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; RAR: retinoic-acid receptor; RORγt: RAR-related orphan receptor gamma t; SAMP8: senescence-accelerated mouse prone 8 strain; TGF-ß: tumor growth factor-ß; TLRs: toll-like receptors.

Innate immunity related pathogen recognition receptors and chronic hepatitis B infection.

Innate immunity consists of several kinds of pathogen recognition receptors (PRRs), which participate in the recognition of pathogens and consequently activation of innate immune system against pathogens. Recently, several investigations reported that PRRs may also play key roles in the induction/stimulation of immune system related complications in microbial infections. Hepatitis B virus (HBV), as the main cause of viral hepatitis in human, can induce several clinical forms of hepatitis B and also might be associated with hepatic complications such as cirrhosis and hepatocellular carcinoma (HCC). Based on the important roles of PRRs in the eradication of microbial infections including viral infections and their related complications, it appears that the molecules may be a main part of immune responses against viral infections including HBV and participate in the HBV related complications. Thus, this review article has brought together information regarding the roles of PRRs in immunity against HBV and its complications.

Toll like receptor 4: an important molecule in recognition and induction of appropriate immune responses against Chlamydia infection.

Chlamydia species are obligate intracellular pathogens causing different infectious diseases particularly asymptomatic genital infections and are also responsible for a wide range of complications. Previous studies showed that there are different immune responses to Chlamydia species and their infections are limited to some cases. Moreover, Chlamydia species are able to alter immune responses through modulating the expression of some immune system related molecules including cytokines. Toll like receptors (TLRs) belonge to pathogen recognition receptors (PRRs) and play vital roles in recognition of microbes and stimulation of appropriate immune responses. Therefore, it appears that TLRs may be considered as important sensors for recognition of Chlamydia and promotion of immune responses against these bacterial infections. Accordingly, TLR4 detects several microbial PAMPs such as bacterial lipopolysacharide (LPS) and subsequently activates transcription from pro-inflammatory cytokines in both MYD88 and TRIF pathways dependent manner. The purpose of this review is to provide the recent data about the status and major roles played by TLR4 in Chlamydia species recognition and promotion of immune responses against these infections and also the relationship between TLR4 activities and pathogenesis of Chlamydia infections.

TGF-ß in Toxoplasmosis: Friend or foe?

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan causing several forms of toxoplasmosis in humans. The main mechanisms that allow the development of the prolonged forms of the disease and its subsequent pathology are yet to be clarified. However, many researchers have hypothesized that immunological and genetic parameters may play crucial roles in the etiology of the disease. Transforming growth factor beta (TGF-ß) is a cytokine with a dual role in the regulation of immune responses including those against parasites. However, the relationship between TGF-ß and immune responses against T .gondii are not fully understood. The important roles played by TGF-ß in the development of Th17 and T regulatory lymphocytes, mucosal immunity and regulation of immune responses have been documented and this provides insights into TGF-ß function during parasitic infections such as toxoplasmosis. Therefore, the aim of this review is to collate the current information regarding the status and association of TGF-ß with T. gondii infection.

Significant roles played by interleukin-10 in outcome of pregnancy.

Imbalanced immune responses against fetus alloantigens can lead to abnormality in pregnancy. Interleukin-10 (IL-10) plays key roles in regulation of immune responses against self and foreign antigens to induce tolerance to these antigens. Therefore, alteration in expression of IL-10 during pregnancy may result in several pathologic conditions such as preterm labor. IL-10 leads to a normal pregnancy via several molecular mechanisms including development of tolerogenic dendritic cells, T regulatory lymphocytes and activation of the JAK1/STAT3 pathway in the target cells. This review has collected recent data regarding the status of IL-10 expression during term and preterm deliveries and also its molecular mechanisms that lead to a normal pregnancy.

A Diagnostic and Symptomatological Study on Trichomoniasis in Symptomatic Pregnant Women in Rafsanjan, South Central Iran in 2012-13.

BACKGROUND: Trichomonas vaginalis, the causative agent of trichomoniasis, is responsible for more than half of all sexually transmitted infections (STIs). The present study aimed to determine the frequency of T. vaginalis infection and its clinical manifestations in symptomatic pregnant women in the area based on four different diagnostic methods. METHODS: A total of 162 pregnant women with at least one sign or symptom of vaginosis, referred to two gynecologic and obstetrics clinics in Rafsanjan City, south central Iran, were randomly selected in 2012-13. Through speculum examination of patients by gynecologists, clinical diagnosis determined, vaginal discharge were collected by using two sterile cotton swabs from the posterior fornix and vagina pH was measured. Samples were examined by three diagnostic methods including wet mount, culture in TYI-S-33 medium and polymerase chain reaction (PCR). RESULTS: T. vaginalis was detected in 19.5%, 27.2%, 56.2% and 51.6% of subjects according to diagnostic methods of clinical diagnosis, wet mount, culture and PCR, respectively. There was statistically significant relationship between T. vaginalis infection and patients' age, gestational age, marriage age, residence, educational level, parity. The symptomatological pattern in the 91 women infected with T. vaginalis was as follows: leukorrhea, 96.7%; urine frequency, 65.9%; odorous secretion, 63.3%; urogenital itching and irritation, 53.8%; vaginal inflammation, 47.3%; dyspareunia, 39.6%; and dysuria, 16.5%. CONCLUSION: Our results indicated a high prevalence of T. vaginalis in symptomatic pregnant women, very low sensitivity and relative high specificity of clinical diagnosis and wet mount technique compared to culture and PCR, as well as thatpregnancy increases the susceptibility to the infection in a gestational age-dependent manner.

Levels of Transforming Growth Factor-Beta After Immunization of Mice With in vivo prepared Toxoplasma gondii Excretory/Secretory Proteins.

BACKGROUND: Zoonotic parasite Toxoplasma gondii has a high prevalence in human populations. A suitable vaccine for animals can stop the transmission of infection between animal and human. OBJECTIVES: The aim of this study was to evaluate in vivo prepared excretory/secretory antigens (E/SA) as a potential candidate for immunization against the parasite and its effect on the production of transforming growth factor-beta (TGF-ß). MATERIALS AND METHODS: Toxoplasma gondii tachyzoites were inoculated in the peritoneal cavity of mice and E/SA was harvested and used in animal immunization with and without adjuvant. Serum levels of anti-E/SA antibodies and TGF-ß were measured in days 0, 3, 7, 14, 28 and 56 after immunization using ELISA technique. The measurements were statistically analyzed. RESULTS: Our results showed that the serum levels of anti-E/SA immunoglobulins significantly increased in all of the immunized groups. The differences of the serum levels of TGF-ß between the groups were statistically significant at days 28 and 56 after immunization with E/SA. CONCLUSIONS: Based on our study, in vivo prepared E/SA may be considered as a good candidate for animal immunization.

The frequency of CCR5 promoter polymorphisms and CCR5 Δ 32 mutation in Iranian populations.

Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (Δ 32) in the exon 1 of the CCR5 gene, which is known as CCR5 Δ 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 Δ 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

Toll-like receptor 4 and hepatitis B infection: molecular mechanisms and pathogenesis.

Hepatitis B virus (HBV) infection mainly causes liver disease, including inflammation, cirrhosis, and hepatocellular carcinoma (HCC). It has been documented that prolonged hepatitis B-infected patients are unable to clear HBV from hepatocytes completely. Previous investigations have suggested that various genetic and immunologic parameters may be responsible for the induction of prolonged infection forms. Toll-like receptors (TLRs), as members of pathogen recognition receptors (PRRs), play critical roles in the recognition of viruses and the induction of appropriate immune responses. Thus, TLRs may be considered as essential sensors for the recognition of HBV and the induction of immune responses against this virus. It has been documented that TLR4 plays key roles in the detection of several microbial pathogen-associated molecular pattern molecules, including bacterial lipopolysaccharide (LPS), as well as endogenous ligands (damage-associated molecular pattern molecules) and subsequently activates pro-inflammatory transcription factors in either MYD88 or TRIF dependent pathways. Previous investigations have proposed that TLR4 might be involved in appropriate immune responses against HBV. Therefore, the aim of this review is to present the recent data regarding the important roles of TLR4 in HBV recognition and regulation of immune responses against this virus, and also its roles in the pathogenesis of cirrhosis and HCC as complications of prolonged hepatitis B infections.

TLR4 in Toxoplasmosis; friends or foe?

Toxoplasma species are obligate intracellular protozoan which are responsible for induction of several forms of Toxoplasmosis in humans. The mechanisms responsible for the progression of the prolonged forms of Toxoplasmosis and associated pathologies are yet to be identified. However, previous studies proposed that immunological and genetic parameters may play important roles in the etiology and complexity of Toxoplasmosis. Pathogen recognition receptors (PRRs) recognize microbial antigens and induce immune responses against parasites, including toxoplasma species. Toll like receptors (TLRs) are PRRs which recognize toxoplasma as a pathogenic parasite and activate immune cells. It has been reported that the TLR4 is a critical innate immune cell receptor in toxoplasma detection and subsequently activates immune responses using either MYD88 or TRIF pathways. This review collates recent information regarding the role of TLR4 and its related signaling molecules with Toxoplasmosis.

Mutations within the HBc gene of the hepatitis B virus: a study on Iranian patients.

BACKGROUND: Hepatitis B virus (HBV) is a serious risk factor for several severe liver diseases such as cirrhosis and hepatocellular carcinoma. HBV, like other viruses, uses several mechanisms to escape from specific immune responses including the use of mutations in the genome which lead to epitope variations. There are several immune responses, including T helper cells, cytotoxic T lymphocytes, and B cells, against the core antigen of HBV (HBcAg) that can lead to HBV eradication. Therefore, mutations within the HBc gene can lead to escape from immune responses by HBV and, hence, understanding the prevalence of HBc mutations among a specific population can be helpful for future treatment and vaccination. This review addresses the recent information regarding the prevalence of mutations within the HBc gene among Iranian HBV infected patients. METHODS: The data presented here was collected gene sequences reported from Iran to the NCBI nucleotide Gen Bank. RESULTS: Results showed that the prevalence of HBc gene mutations is frequent in Iranian HBV infected patients. CONCLUSIONS: Based on our searches it seems that escape from immune responses is a plausible reason for the high prevalence of HBc gene mutations among Iranian HBV infected patients.

Significant roles played by IL-10 in Chlamydia infections.

Chlamydia species are obligate intracellular parasites which cause usually asymptomatic genital tract infections and also are associated with several complications. Previous studies demonstrated that immune responses to Chlamydia species are different and the diseases will be limited to some cases. Additionally, Chlamydia species are able to modulate immune responses via regulating expression of some immune system molecules including cytokines. IL-10, as the main anti-inflammatory cytokine, plays important roles in the induction of immune-tolerance against self-antigen and also immune-homeostasis after microbe elimination. Furthermore, it has been documented that ectopic expression of IL-10 is associated with several chronic infectious diseases. Therefore, it can be hypothesized that changes in the regulation of this cytokine can be associated with infection with several species of Chlamydia and their associated complications. This review collected the recent information regarding the association and relationship of IL-10 with Chlamydia infections. Another aim of this review article is to address recent data regarding the association of genetic variations (polymorphisms) of IL-10 and Chlamydia infections.

NK cells in hepatitis B virus infection: a potent target for immunotherapy.

Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious agents that lead to liver disease in humans. Hepatocellular carcinoma (HCC) and cirrhosis of the liver are the most serious complications arising from prolonged forms of hepatitis B. Previous studies demonstrated that patients suffering from long-term HBV infections are unable to eradicate HBV from hepatocytes completely. The mechanisms responsible for progression of these forms of infection have not yet been clarified. However, it seems that there are differences in genetic and immunological parameters when comparing patients to subjects who successfully clear HBV infections, and these may represent the causes of long-term infection. Natural killer (NK) cells, the main innate immune cells that target viral infections, play important roles in the eradication of HBV from hepatocytes. NK cells carry several stimulatory and inhibitor receptors, and binding of receptors with their ligands results in activation and suppression of NK cells, respectively. The aim of this review is to address the recent information regarding NK cell phenotype, functions and modifications in hepatitis B. This review addresses the recent data regarding the roles of NK cells as novel targets for immunotherapies that target hepatitis B infection. It also discusses the potential to reduce the risk of HCC or cirrhosis of the liver by targeting NK cells.

Important roles played by TGF-ß in hepatitis B infection.

Hepatitis B virus (HBV) which includes, fulminant, acute, chronic, asymptomatic, and occult HBV infection is the most prevalent virus that leads to human liver diseases. Chronic, asymptomatic, and occult infection can induce further sever diseases such as hepatocellular carcinoma (HCC) and cirrhosis of the liver. The underlying mechanisms that allow progression of the prolonged forms of the infection and subsequent HCC or cirrhosis of the liver are yet to be clarified. However, many researchers have suggested that immunological and genetic parameters may play important roles in the etiology of hepatitis B. Transforming growth factor beta (TGF-ß) is an important cytokine with dual regulatory functions in the immune system and in the responses against viral infections. However, the pathways and mechanisms controlling these are not fully understood. The crucial roles of TGF-ß in the development of Th17 and T regulatory lymphocytes, the main cell types involved in autoimmunity and destructive immune related diseases, have been documented and this provides insights into TGF-ß function during hepatitis infection and subsequent HCC and cirrhosis of the liver. Recent findings also confirm that TGF-ß directly alters hepatocyte function during hepatitis B, hence, the aim of this review is to address the current data regarding the association and status of TGF-ß with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.

Molecular and serological detection of acute and latent toxoplasmosis using real-time PCR and ELISA techniques in blood donors of rafsanjan city, iran, 2013.

BACKGROUND: The differentiation between acute and latent forms of the Toxoplasma gondii (T. gondii) infection is still considered as a complicated issue. This study was aimed to elucidate the status of infection in the blood donors and the probable importance of blood transfusion in the transmission of the infection through detecting both immunological and genetic markers of acute and latent infection. METHODS: Totally 235 blood samples from blood donors were collected. The levels of anti-T. gondii IgG and IgM antibodies were examined by specific ELISA kits. cDNA were synthesized from total extracted mRNA molecules from the serum samples and SAG1 gene, specific for tachyzoite form, were amplified using Real-Time PCR technique. Demographic information of study subjects including their gender, age, job, and habitat were recorded. RESULTS: Out of 235 serum samples, 80 (34.04%) and 4 (1.71%) were positive regarding anti-T. gondii IgG and IgM antibodies, respectively. Real-Time PCR results showed that 14 out of 200 (6.97%) of blood donor had mRNA molecules of SAG1 gene. The positive results of Real-Time PCR of SAG1 in female gender and housekeepers were significantly higher than those of male gender and other job categories. CONCLUSION: The prevalence of chronic and acute infection is high in Iranian blood donors. Additionally, evaluation of antibodies could not be reliable, because several donors negative for anti-T. gondii IgM antibodies had detectable SAG1 mRNA molecules. Hence, it seems that molecular diagnostic tests are essential to detect acute infections.

Is the CCR5 Δ 32 mutation associated with immune system-related diseases?

Hypersensitivity and autoimmunity are the main features of immune system-related diseases such as type 2 diabetes (T2D), multiple sclerosis (MS), and asthma. It has been established that chemokines play key roles in the activation and regulation of immune cell migration which is important in the pathogenesis of the diseases mentioned. CC chemokines receptor 5 or CCR5 is a receptor for RANTES, MIP-1α, and MIP-1ß and is expressed by several immune cells including NK cells, T lymphocytes, and macrophages. It plays key roles in the regulation of migration and activation of the immune cells during immune responses against microbe and self-antigens during autoimmunity and hypersensitivity disorders. Therefore, any alteration in the sequence of CCR5 gene or in its expression could be associated with immune system-related diseases. Previous studies revealed that a 32-base pair deletion (Δ 32) in exon 1 of the CCR5 gene led to downregulation of the gene. Previous studies demonstrated that not only CCR5 expression was altered in autoimmune and hypersensitivity disorders, but also that the mutation is associated with the diseases. This review addresses the recent information regarding the association of the CCR5 Δ 32 mutation in immune-related diseases including T2D with and without nephropathy, MS, and asthma. Based on the collected data, it seems that the CCR5 Δ 32 mutation can be considered as a risk factor for MS, but not asthma and T2D with and without nephropathy.