Comparative Occurrence of TLR3 and TLR7 Polymorphisms among Healthy Individual of Various Population

Background: Toll-like receptors (TLRs) act as mediators of an innate immune response to infectious agents. The risk for chronic infection and the development of cancer can be potentially influenced by the genetic variations in the TLR genes. TLR3 and TLR7 genes have been associated with susceptibility to several infections and immune diseases. Human population is very diverse. There are significant variations in the TLR3 and TLR7 polymorphisms among ethnic groups. Variations within the population are associated with the disease outcome. Hence, we aimed to compare the occurrence of TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms among healthy individuals of various populations. Method: Genotyping TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms were done in 158 healthy controls from Western India by utilization of PCR-RFLP. Result: In our study population, the prevalence of TLR3 rs5743312 CC, CT, and TT genotypes were found to be 67.1%, 31.0%, and 1.9%, respectively, whereas genotype distribution of rs3775296 C/A polymorphism was 65.2%, 31.6%, and 3.2%, respectively, and rs3775291C/T was 59.5%, 32.3% and 8.2%, respectively. The occurrence of TLR7 rs179008AA, rs179008AT, rs179008TT genotypes and rs179008A, rs179008T alleles in the healthy individuals were found to be 81.0%, 16.5%, 2.5% and 89.24%, 10.75%, respectively. The prevalence of TLR7 rs179009AA, rs179009AG, rs179009GG genotypes and rs179009A, rs179009G alleles in healthy individuals were 63.3%, 29.1%, 7.6% and 63.3%, 36.7%, respectively. The frequency of TLR7 polymorphism was compared with Italian, Asian, European, African, German, and France populations. The frequency of TLR3 polymorphism was compared with Asians, Caucasians, Taiwanese, Caucasians and Saudi Arabians, Poland, Taiwanese, Italy, Taiwan, Estonia, Asia, and the Caucasus. The inter-population differences were observed in the distribution of TLR3 and TLR7 polymorphisms. Conclusion: The prevalence of TLR3 and TLR7 polymorphisms suggested that genotype-phenotype studies should be conducted among population to address the innate immune responses against pathogens.

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Infection triggers tumor regression through activation of innate immunity in Drosophila

10.1101/552869 ◽

2019 ◽

Author(s):

Camille Jacqueline ◽

Jean-Philippe Parvy ◽

Dominique Faugère ◽

François Renaud ◽

Dorothée Missé ◽

...

Keyword(s):

Immune Responses ◽

Tumor Size ◽

Bacterial Infections ◽

Tumor Regression ◽

Acute Infection ◽

Innate Immune ◽

Immune Gene ◽

Infectious Agents ◽

Innate Immune Responses

AbstractThe pioneering work of Dr. William Coley has shown that infections can stimulate the immune system and improve tumor growth control. However, the immune mechanisms responsible for the protective role of infectious agents have still not been identified. Here, we investigated the role of innate immune pathways in tumor regression by performing experimental infections in genetically modified Drosophila that develop invasive neoplastic tumors. After quantifying tumor size, through image processing, and immune gene expression with transcriptomic analyses, we analyzed the link between tumor size and pathogen-induced immune responses thanks to a combination of statistical and mathematical modeling. Drosophila larvae infected with a naturally-occurring bacterium showed a smaller tumor size compared to controls and fungus-infected larvae, thanks to an increase expression of Imd and Toll pathways. Our mathematical model reinforces this idea by showing that repeated acute infection could results in an even higher decrease in tumor size. Thus, our study suggests that infectious agents can induce tumor regression through the alteration of innate immune responses. This phenomenon, currently neglected in oncology, could have major implications for the elaboration of new preventive and immunotherapeutic strategies.One Sentence SummaryBacterial infections can decrease cancer cell accumulation through stimulation of innate immune responses.

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Contribution of the ACE (rs1799752) and CYP11B2 (rs1799998) Gene Polymorphisms to Atrial Fibrillation in the Tunisian Population

Biological Research For Nursing ◽

10.1177/10998004211029376 ◽

2021 ◽

pp. 109980042110293

Author(s):

Ilhem Gouissem ◽

Fatma Midani ◽

Hayet Soualmia ◽

Meryem Bouchemi ◽

Sana Ouali ◽

...

Keyword(s):

Atrial Fibrillation ◽

Gene Polymorphisms ◽

Tunisian Population ◽

Genotype Distribution ◽

Confounding Factors ◽

Pcr Rflp ◽

Study Population ◽

Polymerase Chain ◽

And Control ◽

T Haplotype

Background: This study investigated the association of angiotensin–converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin–angiotensin–aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. Materials and Methods: The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. Results: The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants ( p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39–8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48–21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62–8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22–5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08–11.77]; p < 0.03). Furthermore, the haplotype–based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. Conclusion: Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population.

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The Robust and Modulated Biomarker Network Elicited by thePlasmodium vivaxInfection Is Mainly Mediated by the IL-6/IL-10 Axis and Is Associated with the Parasite Load

Journal of Immunology Research ◽

10.1155/2014/318250 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Allyson Guimarães da Costa ◽

Lis Ribeiro do Valle Antonelli ◽

Pedro Augusto Carvalho Costa ◽

João Paulo Diniz Pimentel ◽

Nadja Pinto Garcia ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Process ◽

Parasite Load ◽

Serum Biomarkers ◽

Innate Immune ◽

Innate Immune Responses ◽

Healthy Individuals ◽

Healthy Donors ◽

Mixed Pattern ◽

Malaria Episodes

Background. Recent studies have shown that the inflammatory process, including the biomarker production, and the intense activation of innate immune responses are greater in the malaria caused byPlasmodium vivaxthan other species. Here, we examined the levels of serum biomarkers and their interaction during acute malaria.Material and Methods. Blood samples were collected fromP. vivax-infected patients at admission and from healthy donors. Levels of serum biomarkers were measured by Cytometric Bead Assay or ELISA.Results.P. vivaxinfection triggered the production of both inflammatory and regulatory biomarkers. Levels of IL-6, CXCL-8, IFN-γ, IL-5, and IL-10 were higher inP. vivax-infected patients than in healthy donors. On the other hand, malaria patients produced lower levels of TNF-α, IL-12p70, and IL-2 than healthy individuals. While the levels of IL-10 and IL-6 were found independent on the number of malaria episodes, higher levels of these cytokines were seen in patients with higher parasite load.Conclusion. A mixed pattern of proinflammatory and regulatory biomarkers is produced inP. vivaxmalaria. Analysis of biomarker network suggests that IL-10 and IL-6 are a robust axis in malaria patients and that this interaction seems to be associated with the parasite load.

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Inflammatory caspases: key regulators of inflammation and cell death

Biological Chemistry ◽

10.1515/hsz-2014-0253 ◽

2015 ◽

Vol 396 (3) ◽

pp. 193-203 ◽

Cited By ~ 43

Author(s):

Daniel Jiménez Fernández ◽

Mohamed Lamkanfi

Keyword(s):

Molecular Mechanisms ◽

Inflammatory Responses ◽

Innate Immune ◽

Infectious Agents ◽

Innate Immune Responses ◽

First Line ◽

Extracellular Release ◽

Microbial Responses ◽

Inflammatory Caspases ◽

Pro Inflammatory Cytokines

Abstract The innate immune system represents the first line of defence against infectious agents, and co-ordinates cellular and molecular mechanisms that result in effective inflammatory and anti-microbial responses against pathogens. Infection and cellular stress trigger assembly of canonical and noncanonical inflammasome complexes that activate the inflammatory caspases-1 and -11, respectively. These inflammatory caspases play key roles in innate immune responses by inducing pyroptosis to halt intracellular replication of pathogens, and by engaging the extracellular release of pro-inflammatory cytokines and danger signals. In addition, the inflammatory caspases-4, -5 and -11 were recently shown to directly bind microbial components. Although the immune roles of caspase-12 are debated, it was proposed to dampen inflammatory responses by interfering with caspase-1 activation and other innate immune pathways. Here, we recapitulate the reported roles of inflammatory caspases with an emphasis on recent insights into their biological functions.

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Analysis of MDR1 Polymorphisms Among HIV-Infected Individuals on ARV Therapy from Western India

10.21203/rs.3.rs-100712/v1 ◽

2020 ◽

Author(s):

HariOm Singh ◽

Dharmesh Samani ◽

Vijay Chauware ◽

T.N Dhole

Keyword(s):

Treatment Outcome ◽

Hiv Infection ◽

Ethnic Disparities ◽

Western India ◽

Multidrug Resistance Protein ◽

Healthy Individuals ◽

Infected People ◽

Pcr Rflp ◽

Resistance Protein ◽

Reduced Risk

Abstract Background: The multidrug resistance protein, MDR1 is involved in the transport of numerous drugs. Polymorphism of MDR1 is linked with the treatment outcome. Antiretroviral (ARV) regimen is being used to manage the progression of HIV infection. Ethnic disparities have been observed in the distribution of MDR1 genotypes.Methods: MDR1 polymorphisms (1236 C/T, 3435 C/T) was genotyped in 34 HIV-infected individuals with ARV-associated hepatotoxicity, 131 HIV-infected individuals without ARV-associated hepatotoxicity, and one-fifty-five healthy individuals by utilization of PCR-RFLP.Results: The incidence of haplotype TC of MDR1 was found to be more in HIV infected individuals with hepatotoxicity than the non-hepatotoxic ones, thus indicating a greater risk for hepatotoxicity severity (OR=1.96, P=0.06). Whereas the haplotypes TT and CC were found to be linked with a reduced risk for hepatotoxicity severity (OR= 0.16, P=0.006; OR= 0.46, P=0.06). A higher occurrence of MDR1 1236TT genotype was seen among patients with hepatotoxicity who consumed alcohol (28.6% versus 14.8%, OR=1.50). In patients with hepatotoxicity on nevirapine, there was an increased incidence of MDR1 1236TT genotype in contrast with efavirenz (21.7% versus 9.1%, OR=2.11). In HIV-infected people on nevirapine, the incidence of MDR1 1236CT, 1236TT genotypes was found to be more as compared to the ones on efavirenz (43.7% versus 33.3%, OR=1.66; 12.6% versus 8.3%, OR=1.96). Also a higher occurrence of MDR1 1236TT genotype was found in the hepatotoxicity cases on nevirapine, who consume alcohol as compared to the alcohol nonusers on nevirapine (40.0% versus 16.67%, OR=2.21).Conclusion: Haplotype TC was associated with the increased severity of hepatotoxicity because of synergistic effect. In the HIV infected individuals on nevirapine who consume alcohol, the presence of MDR1 1236TT and 3435CT genotypes may have a combined effect on vulnerability to hepatotoxicity severity and progression of HIV infection.

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Study on the association SLC2A9 RS12510549 with uric acid and gout in Vietnamese population

Vietnam Journal of Biotechnology ◽

10.15625/1811-4989/18/1/15263 ◽

2020 ◽

Vol 18 (1) ◽

pp. 49-57

Author(s):

Nguyen Tran Minh Thang ◽

Nguyen Doan Tinh ◽

Nong Van Hai ◽

Nguyen Thuy Duong

Keyword(s):

Uric Acid ◽

Genotype Distribution ◽

Genotype Frequencies ◽

Pcr Rflp ◽

Blood Uric Acid ◽

Vietnamese Population ◽

Study Population ◽

The Relationship ◽

Protein Channels ◽

Larger Sample

Gout is the most common form of arthritis in Vietnam and around the world, caused by an excess of blood uric acid levels. The occurrence of gout is influenced by many risk factors such as diet, living and genetic factors. Studies showed gout is associated with polymorphisms located on genes that encode transport protein channels, including SLC2A9 rs12510549. To evaluate the association of polymorphism SLC2A9 rs12510549 to uric acid levels and gout in the Vietnamese population, we genotyped rs12510549 of 519 subjects (168 gout patients and 351 healthy people) by the PCR–RFLP method. The relationship between genotype distribution, the allele frequency of polymorphism with uric acid levels and gout was assessed through statistical methods. The results show that SLC2A9rs12510549 was in accordance with HWE (p> 0.05) and the genotype frequencies of TT, TC and CC were 0.73, 0.25 and 0.02, respectively, confirming the randomness and representation of the study population. The genotype distribution and frequency of the rs12510549 allele were determined unrelated to uric acid levels and gout in the Vietnamese population (p>0.05). Further study with a larger sample size should be implemented to confirm our results on the association of SLC2A9rs12510549 and gout in the Vietnamese population.

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Regulation of innate immune responses by autophagy-related proteins

The Journal of Cell Biology ◽

10.1083/jcb.201002021 ◽

2010 ◽

Vol 189 (6) ◽

pp. 925-935 ◽

Cited By ~ 170

Author(s):

Tatsuya Saitoh ◽

Shizuo Akira

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Immune Responses ◽

Host Defense ◽

Innate Immune ◽

Infectious Agents ◽

Innate Immune Responses ◽

First Line ◽

Cellular Machinery ◽

Related Proteins

Pattern recognition receptors detect microbial components and induce innate immune responses, the first line of host defense against infectious agents. However, aberrant activation of immune responses often causes massive inflammation, leading to the development of autoimmune diseases. Therefore, both activation and inactivation of innate immune responses must be strictly controlled. Recent studies have shown that the cellular machinery associated with protein degradation, such as autophagy, is important for the regulation of innate immunity. These studies reveal that autophagy-related proteins are involved in the innate immune response and may contribute to the development of inflammatory disorders.

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Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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