{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:40:55Z","timestamp":1760136055145,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>The aim of this study was to define the relationship between several environmental, laboratory, and genetic factors, i.e., TLR2 and NLRP3 polymorphisms, and Helicobacter pylori (H. pylori) infection in children, by comparing three different groups of pediatric subjects: H. pylori-induced gastritis, non-H. pylori gastritis, and healthy controls. Our final study sample included 269 children, which were divided into three groups according to the histopathological exam: group 1 with 51 children with H. pylori-induced gastritis, group 2 with 103 children with H. pylori-negative gastritis, and group 3 (control group) with 115 children without any histopathological changes. All children underwent a thorough anamnesis, clinical exam, laboratory tests, and upper digestive endoscopy with gastric biopsy for rapid urease test, histopathological exam, and genetic analysis of TLR2 rs3804099, TLR2 rs3804100, and NLRP3 rs10754558 gene polymorphisms. We noticed a significant association between living conditions and the type of gastritis (p &lt; 0.0001). Both rapid urease and serological tests were significantly associated with the presence of H. pylori (p &lt; 0.0001). The CT variant genotype of TLR2 rs380499 was significantly associated with neutrophil count (p = 0.0325). We noticed a significant association between the CC variant genotype of NLRP3 rs10754558 and leucocytes, neutrophils, eosinophils, as well as ALT (p = 0.0185, p = 0.0379, p = 0.0483, p = 0.0356). Based on these findings, we state that poor living conditions and rural areas represent risk factors for H. pylori infection. The rapid urease test is a reliable diagnostic tool for this infection. CT and TT carriers of TLR2 rs3804099, as well as CC carriers of NLRP3 rs10754558, might display a more severe degree of systemic inflammation.<\/jats:p>","DOI":"10.3390\/children9020121","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T08:09:20Z","timestamp":1642493360000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Innate Immune Responses in Pediatric Patients with Gastritis\u2014A Trademark of Infection or Chronic Inflammation?"],"prefix":"10.3390","volume":"9","author":[{"given":"Lorena Elena","family":"Meli\u021b","sequence":"first","affiliation":[{"name":"Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 38, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2119-1726","authenticated-orcid":false,"given":"Cristina Oana","family":"M\u0103rginean","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 38, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Oana","family":"S\u0103s\u0103ran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 38, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Mocanu","sequence":"additional","affiliation":[{"name":"Department of Pathology, County Emergency Clinical Hospital of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 50, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana Valentina","family":"Ghiga","sequence":"additional","affiliation":[{"name":"Department of Scientific Medical Research Methodology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 38, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Cri\u0219an","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 38, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"B\u0103nescu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, Gheorghe Marinescu Street No. 38, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"ref_1","first-page":"297","article-title":"The Cytokine Response in THP-1 (Monocyte) and HL-60 (Neutrophil-Differentiated) Cells Infected with Different Genotypes of Helicobacter Pylori Strains","volume":"26","author":"Tokman","year":"2015","journal-title":"Turk. J. Gastroenterol. Off. J. Turk. Soc. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.4062\/biomolther.2020.192","article-title":"Interruption of Helicobacter Pylori-Induced NLRP3 Inflammasome Activation by Chalcone Derivatives","volume":"29","author":"Choi","year":"2021","journal-title":"Biomol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Meli\u021b, L.E., M\u0103rginean, C.O., M\u0103rginean, C.D., and M\u0103rginean, M.O. (2019, February 09). The Relationship between Toll-like Receptors and Helicobacter Pylori-Related Gastropathies: Still a Controversial Topic. Available online: https:\/\/www.hindawi.com\/journals\/jir\/2019\/8197048\/abs\/.","DOI":"10.1155\/2019\/8197048"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"S\u0103s\u0103ran, M.O., Meli\u021b, L.E., and Dobru, E.D. (2021). MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter Pylori. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031406"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"ftu024","DOI":"10.1093\/femspd\/ftu024","article-title":"Helicobacter Pylori Induces IL-1\u03b2 and IL-18 Production in Human Monocytic Cell Line through Activation of NLRP3 Inflammasome via ROS Signaling Pathway","volume":"73","author":"Li","year":"2015","journal-title":"Pathog. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1177\/1753425915619475","article-title":"Activation of NLRP3 Inflammasome in Human Neutrophils by Helicobacter Pylori Infection","volume":"22","author":"Torres","year":"2016","journal-title":"Innate Immun."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"M\u0103rginean, C.O., Meli\u021b, L.E., and S\u0103s\u0103ran, M.O. (2021). Gastric Microenvironment-A Partnership between Innate Immunity and Gastric Microbiota Tricks Helicobacter Pylori. J. Clin. Med., 10.","DOI":"10.3390\/jcm10153258"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/cei.13167","article-title":"NLRP3 Inflammasome Activation Contributes to the Pathogenesis of Rheumatoid Arthritis","volume":"194","author":"Guo","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12943-018-0900-3","article-title":"Role of the NLRP3 Inflammasome in Cancer","volume":"17","author":"Moossavi","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00335-018-9783-2","article-title":"NLRP3 Inflammasome in Colitis and Colitis-Associated Colorectal Cancer","volume":"29","author":"Perera","year":"2018","journal-title":"Mamm. Genome Off. J. Int. Mamm. Genome Soc."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Israel, D., and Peek, R. (2018). Mechanisms of Helicobacter Pylori-Induced Gastric Inflammation. Physiology of the Gastrointestinal Tract, Academic Press.","DOI":"10.1016\/B978-0-12-809954-4.00063-3"},{"key":"ref_12","first-page":"267","article-title":"Mechanisms of Inflammasome Signaling, MicroRNA Induction and Resolution of Inflammation by Helicobacter Pylori","volume":"421","author":"Pachathundikandi","year":"2019","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_13","first-page":"3594","article-title":"Caspase-1 Has Both Proinflammatory and Regulatory Properties in Helicobacter Infections, Which Are Differentially Mediated by Its Substrates IL-1\u03b2 and IL-18","volume":"188","author":"Hitzler","year":"2012","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.3389\/fimmu.2020.01121","article-title":"Unveiling the Crucial Role of Type IV Secretion System and Motility of Helicobacter Pylori in IL-1\u03b2 Production via NLRP3 Inflammasome Activation in Neutrophils","volume":"11","author":"Jang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and Regulation of NLRP3 Inflammasome Activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/ni1112","article-title":"Toll-like Receptor Control of the Adaptive Immune Responses","volume":"5","author":"Iwasaki","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1001\/jama.2013.4350","article-title":"Identification of Genetic Loci Associated with Helicobacter Pylori Serologic Status","volume":"309","author":"Mayerle","year":"2013","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3748\/wjg.v18.i11.1235","article-title":"Polymorphisms of the TLR2 and TLR4 Genes Are Associated with Risk of Gastric Cancer in a Brazilian Population","volume":"18","author":"Silva","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Garza-Gonzalez, E., Bosques-Padilla, F.J., Mendoza-Ibarra, S.I., Flores-Gutierrez, J.P., Maldonado-Garza, H.J., and Perez-Perez, G.I. (2007). Assessment of the Toll-like Receptor 4 Asp299Gly, Thr399Ile and Interleukin-8 -251 Polymorphisms in the Risk for the Development of Distal Gastric Cancer. BMC Cancer, 7.","DOI":"10.1186\/1471-2407-7-70"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"481972","DOI":"10.1155\/2015\/481972","article-title":"Effect of Helicobacter Pylori Eradication on TLR2 and TLR4 Expression in Patients with Gastric Lesions","volume":"2015","author":"Cadamuro","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/00000478-199610000-00001","article-title":"Classification and Grading of Gastritis. The Updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994","volume":"20","author":"Dixon","year":"1996","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_22","first-page":"405","article-title":"Helicobacter Pylori Infection in Children of Texas","volume":"31","author":"Opekun","year":"2000","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1136\/gut.39.1.18","article-title":"Helicobacter Pylori Infection in Children: Relation with Current Household Living Conditions","volume":"39","author":"McCallion","year":"1996","journal-title":"Gut"},{"key":"ref_24","first-page":"e21985","article-title":"Pediatric Gastritis and Its Impact on Hematologic Parameters","volume":"11","author":"Mocan","year":"2020","journal-title":"Medicine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1158\/1055-9965.EPI-11-0702","article-title":"Genetic Variants of Toll-like Receptor 2 and 5, Helicobacter Pylori Infection, and Risk of Gastric Cancer and Its Precursors in a Chinese Population","volume":"20","author":"Zeng","year":"2011","journal-title":"Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol."},{"key":"ref_26","first-page":"311","article-title":"Genetic Polymorphisms of Viral Infection-Associated Toll-like Receptors in Chinese Population","volume":"150","author":"Cheng","year":"2007","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/hel.12067","article-title":"Toll-like Receptors and Cytokines Are Upregulated during Helicobacter Pylori Infection in Children","volume":"18","author":"Torres","year":"2013","journal-title":"Helicobacter"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/hel.12008","article-title":"Helicobacter Pylori Induces Increased Expression of Toll-like Receptors and Decreased Toll-Interacting Protein in Gastric Mucosa That Persists throughout Gastric Carcinogenesis","volume":"18","author":"Afonso","year":"2013","journal-title":"Helicobacter"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Neuper, T., Frauenlob, T., Sarajlic, M., Posselt, G., Wessler, S., and Horejs-Hoeck, J. (2020). TLR2, TLR4 and TLR10 Shape the Cytokine and Chemokine Release of H. Pylori-Infected Human DCs. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113897"},{"key":"ref_30","first-page":"384","article-title":"Single-Nucleotide Polymorphisms in Toll-like Receptor Genes Are Associated with the Prognosis of Gastric Cancer and Are Not Associated with Helicobacter Pylori Infection","volume":"73","author":"Zhao","year":"2019","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Casta\u00f1o-Rodr\u00edguez, N., Kaakoush, N.O., Goh, K.-L., Fock, K.M., and Mitchell, H.M. (2013). The Role of TLR2, TLR4 and CD14 Genetic Polymorphisms in Gastric Carcinogenesis: A Case-Control Study and Meta-Analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060327"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4103\/ijmm.IJMM_20_164","article-title":"Association of Toll-like Receptors 2, 4, 9 and 10 Genes Polymorphisms and Helicobacter Pylori-Related Gastric Diseases in Saudi Patients","volume":"38","author":"Eed","year":"2020","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/CEJ.0000000000000347","article-title":"Genetic Polymorphisms in TLR1, TLR2, TLR4, and TLR10 of Helicobacter Pylori-Associated Gastritis: A Prospective Cross-Sectional Study in Thailand","volume":"27","author":"Tongtawee","year":"2018","journal-title":"Eur. J. Cancer Prev. Off. J. Eur. Cancer Prev. Organ. ECP"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1523-5378.2009.00659.x","article-title":"Toll-like Receptor 4 +3725 G\/C Polymorphism, Helicobacter Pylori Seropositivity, and the Risk of Gastric Atrophy and Gastric Cancer in Japanese","volume":"14","author":"Hishida","year":"2009","journal-title":"Helicobacter"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1002\/eji.201243281","article-title":"The Cag Pathogenicity Island and Interaction between TLR2\/NOD2 and NLRP3 Regulate IL-1\u03b2 Production in Helicobacter Pylori Infected Dendritic Cells","volume":"43","author":"Kim","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1172\/JCI79337","article-title":"Helicobacter Urease-Induced Activation of the TLR2\/NLRP3\/IL-18 Axis Protects against Asthma","volume":"125","author":"Koch","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1152\/physrev.00039.2009","article-title":"Role of Innate Immunity in Helicobacter Pylori-Induced Gastric Malignancy","volume":"90","author":"Peek","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.canlet.2013.07.034","article-title":"Interleukin-1\u03b2 Induced by Helicobacter Pylori Infection Enhances Mouse Gastric Carcinogenesis","volume":"340","author":"Shigematsu","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhao, J., Pan, K., Wang, W., Chen, J., Wu, Y., Lv, L., Li, J., Chen, Y., Wang, D., and Pan, Q. (2012). The Prognostic Value of Tumor-Infiltrating Neutrophils in Gastric Adenocarcinoma after Resection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033655"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29762","DOI":"10.1038\/srep29762","article-title":"Persisting and Increasing Neutrophil Infiltration Associates with Gastric Carcinogenesis and E-Cadherin Downregulation","volume":"6","author":"Fu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1523-5378.2009.00711.x","article-title":"A Population-Based Epidemiologic Study of Helicobacter Pylori Infection and Its Association with Systemic Inflammation","volume":"14","author":"Jackson","year":"2009","journal-title":"Helicobacter"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jcla.21669","article-title":"Association of Neutrophil to Lymphocyte Ratio with Presence and Severity of Gastritis Due to Helicobacter Pylori Infection","volume":"28","author":"Farah","year":"2014","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_43","unstructured":"Atayan, Y., and Hacisalihoglu, P. (2017). The Correlation between Tissue Helicobacter Pylori Severity and the Increase in Serum Neutrophil\/Lymphocyte Ratio in Patients with Active Chronic Gastritis. Biomed. Res., 28."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e16188","DOI":"10.1097\/MD.0000000000016188","article-title":"The Usefulness of Inflammatory Biomarkers in Diagnosing Child and Adolescent\u2019s Gastritis: STROBE Compliant Article","volume":"98","author":"Mocan","year":"2019","journal-title":"Medicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1046\/j.1468-3083.2002.00497.x","article-title":"The Link between Helicobacter Pylori Infection and Rosacea","volume":"16","author":"Szlachcic","year":"2002","journal-title":"J. Eur. Acad. Dermatol. Venereol. 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