Assessment of some immune markers in typhoid-patients
A case control study
Keywords:
Salmonella typhi, Immune response, IL-4, IL-17, CD8, CD22Abstract
A case-control study was carried out in the General Teaching Hospital in Balad City, Iraq. Eighty-eight male and female were included in this study; 58 typhoid-patients infected with S.typhi and 30 healthy individuals as controls. Acute typhoid-patients have been diagnosed according to positive blood culture and IgM and chronic typhoid-patients have been diagnosed according to positive stool culture and IgG. Four immunological markers have been measured in all individuals' serum; interleukin 4 (IL-4), interleukin 17 (IL-17), cluster of differentiation 8 (CD 8) and cluster of differentiation 22 (CD 22) using an Enzyme-Linked Immunosorbent Assay (ELISA). We diagnosed 32 and 26 patients infected with acute and chronic infection respectively, the results proved a significant increase (P-value=<0.05) in all markers in acute and chronic infections as compare with control. A significant differences P-value (0.0003 and <0.0001) has been proved between acute and chronic infection in IL-4 and IL-17 respectively. While, there was no significant differences P-value (0.13 and 0.32) between acute and chronic infection in CD8 and CD22 respectively. Conclusions: IL-4, IL-17, CD8 and CD22 serum levels increase in typhoid-patients caused by S.typhi in humans.
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Abd-Aljabar, E.M., Aljanaby, A.A.J., 2021. Role of macrophage migration inhibitory factor, cluster of differentiation 19 and interleukin 23 in individuals infected with Salmonella typhi. J. Exp. Biolo. Agric. Sci. 9 (3), 394–400. https://doi.org/ 10.18006/2021.9(3).394.400.
Adam, R.W., Al-Labban, H.M.Y., Aljanaby, A.A.J. and Abbas, N.A., 2019. Synthesis, Characterization and Antibacterial Activity of Some Novel 1, 2, 3-Triazol-Chalcone Derivatives from N-Acetyl-5H-Dibenzo [b, f] Azepine-5-Carboxamide. Nano Biomed. Eng, 11(2), pp.99-110. doi: 10.5101/nbe.v11i2.p99-110.
Afzal, R.K., Khalid, F., Hannan, A. and Ahmed, S.A., 2019. Methylglyoxal: Antimicrobial activity against blood culture isolates of Salmonella Typhi and other Gram negative rods. Pakistan journal of medical sciences, 35(4), p.1110. doi: 10.12669/pjms.35.4.807
Alhasnawi, H.M.R.J. and Aljanaby, A.A.J., 2022. The immunological role of CD4 and CD8 in patients infected with Helicobacter pylori and stomach cancer. Gene Reports, 26, p.101500. doi.org/10.1016/j.genrep.2022.101500
Aljanaby, A.A.J., Al-Faham, Q.M.H., Aljanaby, I.A.J. and Hasan, T.H., 2022. Epidemiological study of Mycobacterium Tuberculosis in Baghdad Governorate, Iraq. Gene Reports, (26):1-5.101467. https://doi.org/10.1016/j.genrep.2021.101467
Aljanaby, A.A.J. and Alhasnawi, H.M.R.J., 2017. Research article phenotypic and molecular characterization of multidrug resistant Klebsiella pneumoniae isolated from different clinical sources in Al-Najaf Province-Iraq. Pak. J. Biol. Sci, 20(5), pp.217-232. doi: 10.3923/pjbs.2017.217.232
Aljanaby, A.A.J. and Aljanaby, I.A.J., 2018. Prevalence of aerobic pathogenic bacteria isolated from patients with burn infection and their antimicrobial susceptibility patterns in Al-Najaf City, Iraq-a three-year cross-sectional study. F1000Research, 7(1157), p.1157. doi: 10.12688/f1000research.15088.1
Aljanaby, A.A.J. and Medhat, A.R., 2017. prevalence of some antimicrobials resistance associated-genes in Salmonella typhi isolated from patients infected with typhoid fever. J. Biol. Sci, 17(4), pp.171-184. doi: 10.3923/jbs.2017.171.184
Bula-Rudas, F.J., Rathore, M.H. and Maraqa, N.F., 2015. Salmonella infections in childhood. Advances in pediatrics, 62(1), pp.29-58. doi: 10.1016/j.yapd.2015.04.005
Clark, E.A. and Giltiay, N.V., 2018. CD22: a regulator of innate and adaptive B cell responses and autoimmunity. Frontiers in immunology, 9, p.2235. doi.org/10.3389/fimmu.2018.02235
Das, S., Chowdhury, R., Pal, A., Okamoto, K. and Das, S., 2019. Salmonella Typhi outer membrane protein STIV is a potential candidate for vaccine development against typhoid and paratyphoid fever. Immunobiology, 224(3), pp.371-382. doi: 10.1016/j.imbio.2019.02.011
Deimel, L.P., Li, Z., Roy, S. and Ranasinghe, C., 2021. STAT3 determines IL-4 signalling outcomes in naïve T cells. Scientific reports, 11(1), pp.1-14. doi: 10.1038/s41598-021-89860-7
De Morales, J.M.G.R., Puig, L., Daudén, E., Cañete, J.D., Pablos, J.L., Martín, A.O., Juanatey, C.G., Adán, A., Montalbán, X., Borruel, N. and Ortí, G., 2020. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: an updated review of the evidence focusing in controversies. Autoimmunity reviews, 19(1), p.102429. doi: 10.1016/j.autrev.2019.102429
DeRoeck, D., Jodar, L. and Clemens, J., 2007. Putting typhoid vaccination on the global health agenda. New England Journal of Medicine, 357(11), pp.1069-1071. doi:10.1056/ NEJMp078144
Dougan, G. and Baker, S., 2014. Salmonella enterica serovar Typhi and the pathogenesis of typhoid fever. Annual review of microbiology, 68, pp.317-336. doi: 10.1146/annurev-micro-091313-103739
Egholm, C., Heeb, L.E., Impellizzieri, D. and Boyman, O., 2019. The regulatory effects of interleukin-4 receptor signaling on neutrophils in type 2 immune responses. Frontiers in immunology, 10, p.2507. doi.org/10.3389/fimmu.2019.02507
Eini, P., Majzoobi, M.M., Ghasemi Basir, H.R., Moosavi, Z. and Moradi, A., 2020. Comparison of the serum level of interleukin‐4 in patients with brucellosis and healthy controls. Journal of clinical laboratory analysis, 34(7), p.e23267. doi: 10.1002/jcla.23267
Ertelt, J.M., Johanns, T.M., Mysz, M.A., Nanton, M.R., Rowe, J.H., Aguilera, M.N. and Way, S.S., 2011. Selective culling of high avidity antigen‐specific CD4+ T cells after virulent Salmonella infection. Immunology, 134(4), pp.487-497. doi: 10.1111/j.1365-2567.2011.03510.x
Feng, J.Y., Rao, G.Z., Liu, Y.P., Li, P., Cui, R., Li, J.H., Liu, J.Z. and Peng, Z.H., 2009. Expression of CD1a and CD207 in condyloma acuminatum epidermis. Xi bao yu fen zi mian yi xue za zhi= Chinese journal of cellular and molecular immunology, 25(5), pp.420-422. https://pubmed.ncbi.nlm.nih.gov/19426597
Fernandes, V.E., Ercoli, G., Bénard, A., Brandl, C., Fahnenstiel, H., Müller-Winkler, J., Weber, G.F., Denny, P., Nitschke, L. and Andrew, P.W., 2020. The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection. PLoS pathogens, 16(4), p.e1008464. doi: 10.1371/journal.ppat.1008464
Fresnay, S., McArthur, M.A., Magder, L., Darton, T.C., Jones, C., Waddington, C.S., Blohmke, C.J., Angus, B., Levine, M.M., Pollard, A.J. and Sztein, M.B., 2016. Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans. Journal of translational medicine, 14(1), pp.1-14. doi: 10.1186/s12967-016-0819-7
Fry, T.J., Shah, N.N., Orentas, R.J., Stetler-Stevenson, M., Yuan, C.M., Ramakrishna, S., Wolters, P., Martin, S., Delbrook, C., Yates, B. and Shalabi, H., 2018. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature medicine, 24(1), pp.20-28. doi: 10.1038/nm.4441
Hadi, H. I. and Aljanaby, A.A.J. 2022. Helicobacter Pylori-Oncogenic Protein Cytotoxin-Associated Gene A and Assessment of CD14 and CD163 in Duodenal Ulcer and Gastric Cancer Patients. International Journal of Health Sciences, 6(S2), 839–851. https://doi.org/10.53730/ijhs.v6nS2.5134
Haas, K.M., Johnson, K.L., Phipps, J.P. and Do, C., 2018. CD22 promotes B-1b cell responses to T Cell–independent type 2 antigens. The Journal of Immunology, 200(5), pp.1671-1681. doi: 10.4049/jimmunol.1701578
Hasan, T.H., Alasedi, K.K. and Aljanaby, A.A.J., 2021. A Comparative Study of Prevalence Antimicrobials Resistance Klebsiella pneumoniae among Different Pathogenic Bacteria Isolated from Patients with Urinary Tract Infection in Al-Najaf City, Iraq. Latin american journal of pharmacy, 40(SI), pp.174-178.
Huang, F.C., 2021. The Interleukins Orchestrate Mucosal Immune Responses to Salmonella Infection in the Intestine. Cells, 10(12), p.3492. doi: 10.3390/cells10123492
Ilkka, S.J., 2018. Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes [J]. Front Immunol, 9, p.888. doi: 10.3389/fimmu.2018.00888
Ingram, J.P., Brodsky, I.E. and Balachandran, S., 2017. Interferon-γ in Salmonella pathogenesis: New tricks for an old dog. Cytokine, 98, pp.27-32. doi: 10.1016/j.cyto.2016.10.009
Iwasaki, T., Hara, H., Takahashi-Igari, M., Matsuda, Y. and Imai, H., 2021. Probable hemophagocytic lymphohistiocytosis by extensively drug-resistant Salmonella Typhi. Pediatrics International: Official Journal of the Japan Pediatric Society. doi: 10.1111/ped.14695.
Jiang, Y.N., Cai, X., Zhou, H.M., Jin, W.D., Zhang, M., Zhang, Y., Du, X.X. and Chen, Z.H.K., 2015. Diagnostic and prognostic roles of soluble CD22 in patients with Gram-negative bacterial sepsis. Hepatobiliary & Pancreatic Diseases International, 14(5), pp.523-529. doi: 10.1016/s1499-3872(15)60394-0
Johnson, R., Mylona, E. and Frankel, G., 2018. Typhoidal Salmonella: Distinctive virulence factors and pathogenesis. Cellular Microbiology, 20(9), p.e12939. doi: 10.1111/cmi.12939
Kumalo, A., Gambura, E., Dodicho, T., Ahmed, K.S., Balcha, T., Beshir, B. and Abraham, M., 2021. Prevalence of intestinal parasites and Salmonella typhi among food handlers working in catering establishments of public institutes found in Dawuro Zone, South-Western Ethiopia. Journal of Parasitology Research, 2021. 13;2021:8889302. doi: 10.1155/2021/8889302
Lanza, F., Maffini, E., Rondoni, M., Massari, E., Faini, A.C. and Malavasi, F., 2020. CD22 expression in b-cell acute lymphoblastic leukemia: Biological significance and implications for inotuzumab therapy in adults. Cancers, 12(2), p.303. doi: 10.3390/cancers12020303
Lopez-Medina, M., Perez-Lopez, A., Alpuche-Aranda, C. and Ortiz-Navarrete, V., 2014. Salmonella modulates B cell biology to evade CD8+ T cell-mediated immune responses. Frontiers in immunology, 5, p.586. doi: 10.3389/fimmu.2014.00586
Majeed, H.T. and Aljanaby, A.A.J., 2019. Antibiotic susceptibility patterns and prevalence of some extended spectrum beta-lactamases genes in gram-negative bacteria isolated from patients infected with urinary tract infections in Al-Najaf City, Iraq. Avicenna journal of medical biotechnology, 11(2), p.192. https://pubmed.ncbi.nlm.nih.gov/31057723/
Männe, C., Takaya, A., Yamasaki, Y., Mursell, M., Hojyo, S., Wu, T.Y., Sarkander, J., McGrath, M.A., Cornelis, R., Hahne, S. and Cheng, Q., 2019. Salmonella SiiE prevents an efficient humoral immune memory by interfering with IgG+ plasma cell persistence in the bone marrow. Proceedings of the National Academy of Sciences, 116(15), pp.7425-7430. doi:10.1073/pnas.1818242116
Marino, S., Beretta, E. and Kirschner, D.E., 2007. The role of delays in innate and adaptive immunity to intracellular bacterial infection. Mathematical Biosciences & Engineering, 4(2), p.261. DOI: 10.3934/mbe.2007.4.261
Mawazo, A., Bwire, G.M. and Matee, M.I., 2019. Performance of Widal test and stool culture in the diagnosis of typhoid fever among suspected patients in Dar es Salaam, Tanzania. BMC research notes, 12(1), pp.1-5. doi: 10.1186/s13104-019-4340-y
McArthur, M.A. and Sztein, M.B., 2012. Heterogeneity of multifunctional IL-17A producing S. Typhi-specific CD8+ T cells in volunteers following Ty21a typhoid immunization. PloS one, 7(6), p.e38408. doi: 10.1371/journal.pone.0038408
Mei, Y., Zhao, L., Liu, Y., Gong, H., Song, Y., Lei, L., Zhu, Y., Jin, Z., Ma, S., Hu, B. and Sun, Q., 2017. Combining DNA vaccine and AIDA-1 in attenuated Salmonella activates tumor-specific CD4+ and CD8+ T-cell responses. Cancer immunology research, 5(6), pp.503-514. doi: 10.1158/2326-6066.CIR-16-0240-T
Medhat, A.R. and Aljanabay, A.A.J. 2022. Epidemiology of Typhoid Fever in Balad City, Iraq. International Journal of Health Sciences, 6(S1), 1049-1063.https://doi.org/10.53730/ijhs.v6nS1.4834
Mohammed, E.H., Aljanaby, A.A.J., 2020. Galectin3 and cd16 play an important immunological role in patients infected with salmonella typhi. International Journal of Research in Pharmaceutical Sciences, 2020, 11(3):4162–4169. doi: https://doi.org/10.26452/ijrps.v11i3.2623
Nograles, K.E., Zaba, L.C., Guttman‐Yassky, E., Fuentes‐Duculan, J., Suárez‐Fariñas, M., Cardinale, I., Khatcherian, A., Gonzalez, J., Pierson, K.C., White, T.R. and Pensabene, C., 2008. Th17 cytokines interleukin (IL)‐17 and IL‐22 modulate distinct inflammatory and keratinocyte‐response pathways. British Journal of Dermatology, 159(5), pp.1092-1102. doi: 10.1111/j.1365-2133.2008.08769.x.
Noto Llana, M., Sarnacki, S.H., Morales, A.L., Aya Castaneda, M.D.R., Giacomodonato, M.N., Blanco, G. and Cerquetti, M.C., 2017. Activation of iNKT cells prevents Salmonella-Enterocolitis and Salmonella-induced reactive arthritis by downregulating IL-17-producing γδT cells. Frontiers in cellular and infection microbiology, 7, p.398. doi: 10.3389/fcimb.2017.00398
Otipoby, K.L., Draves, K.E. and Clark, E.A., 2001. CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1. Journal of Biological Chemistry, 276(47), pp.44315-44322. doi: 10.1074/jbc.M105446200
Qin, H., Ramakrishna, S., Nguyen, S., Fountaine, T.J., Ponduri, A., Stetler-Stevenson, M., Yuan, C.M., Haso, W., Shern, J.F., Shah, N.N. and Fry, T.J., 2018. Preclinical development of bivalent chimeric antigen receptors targeting both CD19 and CD22. Molecular Therapy-Oncolytics, 11, pp.127-137. doi: 10.1016/j.omto.2018.10.00
Rashad, J.M.B.M., Aljanaby, A.A.J., 2021. Role of interleukin-2, interleukin-4 and cluster of differentiation-22 as an immune markers in individuals infected with Helicobacter pylori. J. Exp. Biol. Agric. Sci. 9 (3), 388–393. https://doi.org/10.18006/2021.9 (3).388.393.
Raskov, H., Orhan, A., Christensen, J.P. and Gögenur, I., 2021. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. British Journal of Cancer, 124(2), pp.359-367. doi: 10.1038/s41416-020-01048-4
Reinhart, R. and Kaufmann, T., 2018. IL-4 enhances survival of in vitro-differentiated mouse basophils through transcription-independent signaling downstream of PI3K. Cell death & disease, 9(7), pp.1-12. doi: 10.1038/s41419-018-0754-z.
Sachin, P., Gadani, S.P., Cronk, J.C., Norris, G.T. and Kipnis, J., 2012. Interleukin-4: a cytokine to remember. J Immunol, 189, pp.4213-4421. doi: 10.4049/jimmunol.1202246
Salerno-Goncalves, R., Pasetti, M.F. and Sztein, M.B., 2002. Characterization of CD8+ effector T cell responses in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. The Journal of Immunology, 169(4), pp.2196-2203. doi: 10.4049/jimmunol.169.4.2196
Schäfer, S. and Zernecke, A., 2021. CD8+ T Cells in Atherosclerosis. Cells, 10(1), p.37. doi: 10.3390/cells10010037
Sharma, D., Khan, J. and Agarwal, S., 2021. Salmonella typhi as cause of neonatal sepsis: case report and literature review. The Journal of Maternal-Fetal & Neonatal Medicine, 34(5), pp.732-735. doi: 10.1080/14767058.2019.1614555
Shah, N.N., Highfill, S.L., Shalabi, H., Yates, B., Jin, J., Wolters, P.L., Ombrello, A., Steinberg, S.M., Martin, S., Delbrook, C. and Hoffman, L., 2020. CD4/CD8 T-cell selection affects chimeric antigen receptor (CAR) T-cell potency and toxicity: updated results from a phase I anti-CD22 CAR T-cell trial. Journal of Clinical Oncology, 38(17), p.1938. doi: 10.1200/JCO.19.03279
Sheikh, A., Jackson, J., Shim, H.B., Yau, C., Seo, J.H. and Abraham, N., 2022. Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection. Scientific reports, 12(1), pp.1-14. https://www.nature.com/articles/s41598-021-03936-y
Stott, B., Lavender, P., Lehmann, S., Pennino, D., Durham, S. and Schmidt-Weber, C.B., 2013. Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation. Journal of allergy and clinical immunology, 132(2), pp.446-454. doi: 10.1016/j.jaci.2013.03.050.
Sun, L., Wang, X., Saredy, J., Yuan, Z., Yang, X. and Wang, H., 2020. Innate-adaptive immunity interplay and redox regulation in immune response. Redox Biology, p.101759. doi: 10.1016/j.redox.2020.101759
Sztein, M.B., Salerno-Goncalves, R. and McArthur, M.A., 2014. Complex adaptive immunity to enteric fevers in humans: lessons learned and the path forward. Frontiers in immunology, 5, p.516. doi: 10.3389/fimmu.2014.00516
Takaya, A., Yamamoto, T. and Tokoyoda, K., 2020. Humoral immunity vs. Salmonella. Frontiers in immunology, 10, p.3155. doi: 10.3389/fimmu.2019.03155
Ul-Haq, Z., Naz, S. and Mesaik, M.A., 2016. Interleukin-4 receptor signaling and its binding mechanism: A therapeutic insight from inhibitors tool box. Cytokine & growth factor reviews, 32, pp.3-15. doi: 10.1016/j.cytogfr.2016.04.002
Valeri, M. and Raffatellu, M., 2016. Cytokines IL-17 and IL-22 in the host response to infection. Pathogens and disease, 74(9), p.ftw111. doi.org/10.1093/femspd/ftw111
Vidlak, D. and Kielian, T., 2012. Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection. Journal of neuroinflammation, 9(1), pp.1-12. doi: 10.1186/1742-2094-9-128
Voysey, M., Pant, D., Shakya, M., Liu, X., Colin-Jones, R., Theiss-Nyland, K., Smith, N., Shrestha, S., Basnyat, B., Pollard, A.J. and Pitzer, V.E., 2020. Under-detection of blood culture-positive enteric fever cases: the impact of missing data and methods for adjusting incidence estimates. PLoS neglected tropical diseases, 14(1), p.e0007805. doi: 10.1371/journal.pntd.0007805
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