Expression of IL1β Gene in the Placentas from Humans and Cows during Brucella Infection

Document Type : Original Articles


1 Department of Microbiology, College of Veterinary Medicine, University of Basrah, Basrah, Iraq

2 Department of Medicine, College of Veterinary Medicine, University of Basrah, Basrah, Iraq


Brucellosis is an important contagious disease affecting most domestic and mature animals. Since the impact of IL-1β in B. abortus invasion and survival remains elusive, the current study sought to elucidate the actual roles of these potent cytokines in the modulation of the initial immune response to Brucella infection. Therefore, this study aimed to detect Brucella abortus in the placenta of aborted women and cows and estimate the expression of the interleukin 1β (IL1β) gene associated with immune response mechanisms to Brucella abortus infection. The detection of Brucella abortus was performed by Rose Bengal Test (RBT) and Polymerase Chain Reaction based AlkB gene (AlkB-PCR) in the sera and placenta samples of aborted women and cows, respectively. The overall percentage of Brucella abortus infection was 13.1% and 5% as determined by RBT and AlkB-PCR in aborted women’s sera and placentas, respectively. On the other hand, the overall percentage rates of Brucella abortus infection in the sera and placentas from aborted cows were 30% and 11% as estimated by RBT and AlkB-PCR, respectively. The results of RBT demonstrated that the association between Brucella abortus and abortion in cows was statistically significant. On the other hand, it was found that the association between Brucella abortus and abortion in women was not significant. Moreover, according to the results of AlkB-based PCR, the association between Brucella abortus and abortion was statistically significant in aborted cows, while it was not significant in aborted women. The sensitivity, specificity, and accuracy of RBT were calculated as 60.00, 53.85, and 54.55%, respectively. Moreover, positive and negative predictive values were reported as 14.33% and 91.28%, respectively. Regarding RBT for aborted cows, the sensitivity, specificity, and accuracy of the test were 81.82%, 57.78%, and 62.49%, respectively. The positive predictive value was reported as 32.08%, while the negative predictive value was reported as 92.88%. Quantitative PCR (qPCR) was carried out for the evaluation of Interleukin 1 Beta (IL1β) gene expression. The qPCR result was presented as a fold change in gene expression. A significant increment of IL1β gene expression was observed in aborted women (114.905±99.661) and cows (22.454 ±18.528), compared to non-aborted women (4.953±5.564) and cows (2.033±1.845). Statistical comparison of ILgene expression between aborted women and cows illustrated a non-significant increment in IL1β gene expression in aborted women (114.905±99.661), compared to aborted cows (22.454 ±18.528).


Main Subjects

  1. Smith JA. Brucella lipopolysaccharide and pathogenicity: the core of the matter. Taylor & Francis; 2018. p. 379-82.
  2. Sternon J-F, Godessart P, Gonçalves de Freitas R, Van der Henst M, Poncin K, Francis N, et al. Transposon sequencing of Brucella abortus uncovers essential genes for growth in vitro and inside macrophages. Infect Immun. 2018;86(8):00312-18.
  3. González-Espinoza G, Arce-Gorvel V, Mémet S, Gorvel J-P. Brucella: reservoirs and niches in animals and humans. Pathogens. 2021;10(2):186.
  4. Quinn P, Carter M, Markey B, Carter G. clinical Veterinary Microbiology microbial disease, Black well sciences. Publishing Wolf Spain. 2002;2:261-7.
  5. Jung M, Shim S, Im YB, Park WB, Yoo HS. Global gene-expression profiles of intracellular survival of the BruAb2_1031 gene mutated Brucella abortus in professional phagocytes, RAW 264.7 cells. BMC Microbiol. 2018;18(1):1-14.
  6. Matope G, Bhebhe E, Muma J, Lund A, Skjerve E. Risk factors for Brucella spp. infection in smallholder household herds. Epidemiol Infect. 2011;139(1):157-64.
  7. OIE. Manual of diagnostic tests and vaccines for terrestrial animals. OIE Paris, France; 2008.
  8. Li J-Y, Liu Y, Gao X-X, Gao X, Cai H. TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro. Cell Mol Immunol. 2014;11(5):477-94.
  9. Hielpos MS, Fernández AG, Falivene J, Alonso Paiva IM, Muñoz González F, Ferrero MC, et al. IL-1R and inflammasomes mediate early pulmonary protective mechanisms in respiratory Brucella abortus infection. Front Cell Infect Microbiol. 2018:391.
  10. Lacey CA, Mitchell WJ, Dadelahi AS, Skyberg JA. Caspase-1 and caspase-11 mediate pyroptosis, inflammation, and control of Brucella joint infection. Infect Immun. 2018;86(9):e00361-18.
  11. Gomes MTR, Campos PC, Oliveira FS, Corsetti PP, Bortoluci KR, Cunha LD, et al. Critical role of ASC inflammasomes and bacterial type IV secretion system in caspase-1 activation and host innate resistance to Brucella abortus infection. J Immunol. 2013;190(7):3629-38.
  12. Padilla Poester F, Nielsen K, Ernesto Samartino L, Ling Yu W. Diagnosis of brucellosis. Open Vet J. 2010;4(1).
  13. Terzi G, Büyüktanir Ö, Genç O, Gücükoğlu A, Yurdusev N. Detection of Brucella antibody and DNA in cow milk by ELISA and PCR methods. Kafkas Univ Vet Fak Derg. 2010;16:47-52.
  14. Al-Alo KZ, Mohammed AJ. A cross sectional study on the seroprevalence of bovine brucellosis in Al-Najaf province in Iraq. Iraqi J Vet Med. 2021;35(4):617-20.
  15. Alatabi AC, Al-Alo KZ, Hatem AA, Alatabi AC. Serodiagnosis for brucellosis in camels by rose Bengal and C-ELISA test in Iraq. Ann Trop Med Public Health. 2020.
  16. Al-Jaboury EI, Abdullah FA. Detection of Brucella species in apparently healthy cows and goats raw milk by PCR. Basra J Vet Res. 2018;17(1):176-91.
  17. Hasoon MQ, Al-Amery MA. Prevalence of brucellosis in buffaloes of basra governorate, Basra-Iraq. Basra J Vet Res. 2017;16(1).
  18. Khudhur HR, Menshed AA, Hasan AA. Increasing of Macrophage Migration Inhibitory Factor Expression in Human Patients Infected with Virulent Brucella in Iraq. Microbiol Biotechnol Lett. 2020;48(4):569-73.
  19. Wareth G, Hikal A, Refai M, Melzer F, Roesler U, Neubauer H. Animal brucellosis in Egypt. J Infect Dev Ctries. 2014;8(11):1365-73.
  20. Marianelli C, Martucciello A, Tarantino M, Vecchio R, Iovane G, Galiero G. Evaluation of molecular methods for the detection of Brucella species in water buffalo milk. J Dairy Sci. 2008;91(10):3779-86.
  21. Dahl MO, Hamdoon OK, Abdulmonem ON. Epidemiological Analysis for medical records of Veterinary Teaching Hospital, University of Mosul during 2017 to 2019. Iraqi J Vet Sci. 2021;35(3):541-8.
  22. Probert WS, Schrader KN, Khuong NY, Bystrom SL, Graves MH. Real-time multiplex PCR assay for detection of Brucella spp., B. abortus, and B. melitensis. J Clin Microbiol. 2004;42(3):1290-3.
  23. Kledmanee K, Liabsuetrakul T, Sretrirutchai S. Seropositivities against brucellosis, coxiellosis, and toxoplasmosis and associated factors in pregnant women with adverse pregnancy outcomes: A cross-sectional study. Plos One. 2019;14(5):e0216652.
  24. Ali S, Akhter S, Neubauer H, Scherag A, Kesselmeier M, Melzer F, et al. Brucellosis in pregnant women from Pakistan: an observational study. BMC Infect Dis. 2016;16(1):1-6.
  25. Al-Bayaa YJ. Epidemiology of Human Brucellosis among Populations in Iraq's Provinces in 2015. J Fac Med Baghdad. 2017;59(2):165-9.
  26. Daood II, Zajmi A, Nouri HS, Al Jubory DIH. Seroprevalence of Brucellosis from the city Mosul Iraq. is Int J Psychosoc Rehabilitation. 2020;24(2).
  27. Al-mashhadany DA. Application of rose bengal test for surveillance human brucellosis in Erbil governorate kurdistan region Iraq. 2018.
  28. Shehada A, Abu Halaweh M. Seroprevalence of Brucella species among women with miscarriage in Jordan. East Mediterr Health J. 2011;17(11):871-4.
  29. Gwida M, El-Ashker M, Melzer F, El-Diasty M, El-Beskawy M, Neubauer H. Use of serology and real time PCR to control an outbreak of bovine brucellosis at a dairy cattle farm in the Nile Delta region, Egypt. Ir Vet J. 2015;69(1):1-7.
  30. Sarker M, Begum M, Rahman M, Islam M, Yasmin L, Ehsan M, et al. Conventional pcr based detection of brucella abortus infected cattle in some selected areas of Bangladesh. Bangladesh J Vet Med. 2018;16(1):39-44.
  31. Joyee A, Thyagarajan S, Sowmya B, Venkatesan C, Ganapathy M. Need for specific & routine strategy for the diagnosis of genital chlamydial infection among patients with sexually transmitted diseases in India. Indian J Med Res. 2003;118:152-7.
  32. Lucero N, Ayala S, Escobar G, Jacob N. The value of serologic tests for diagnosis and follow up of patients having brucellosis. Am J Infect Dis. 2007;3(1):27-35.
  33. Rahman M. Experimental infection and protective immunity of Sprague-Dawley rats with Brucella abortus: PhD thesis, College of Veterinary Medicine, Chonbuk National University. 2003.
  34. Chachra D, Saxena HM, Kaur G, Ch M. Comparative efficacy of Rose Bengal plate test, standard
    tube agglutination test and Dot ELISA in immunological detection of antibodies to Brucella abortus in sera. Afr J Microbiol Res. 2009;1(3):030-3.
  1. Zakaria AM. Comparative assessment of sensitivity and specificity of rose bengal test and modified in-house ELISA by using IS711 TaqMan Real Time PCR assay as a gold standard for the diagnosis of bovine brucellosis. Biomed Pharmacol J. 2018;11(2):951-7.
  2. Černyševa M, Knjazeva E, Egorova L. Study of the plate agglutination test with rose bengal antigen for the diagnosis of human brucellosis. Bull World Health Organ. 1977;55(6):669.
  3. Ruiz-Mesa J, Sanchez-Gonzalez J, Reguera J, Martin L, Lopez-Palmero S, Colmenero J. Rose Bengal test: diagnostic yield and use for the rapid diagnosis of human brucellosis in emergency departments in endemic areas. Clin Microbiol Infect. 2005;11(3):221-5.
  4. Amjadi O, Rafiei A, Mardani M, Zafari P, Zarifian A. A review of the immunopathogenesis of Brucellosis. Infect Dis. 2019;51(5):321-33.
  5. Fernández AG, Ferrero MC, Hielpos MS, Fossati CA, Baldi PC. Proinflammatory response of human trophoblastic cells to Brucella abortus infection and upon interactions with infected phagocytes. Biol Reprod. 2016;94(2):48, 1-11.
  6. Löb S, Amann N, Kuhn C, Schmoeckel E, Wöckel A, Kaltofen T, et al. Interleukin-1 beta is significantly upregulated in the decidua of spontaneous and recurrent miscarriage placentas. J Reprod Immunol. 2021;144:103283.
  7. Ali A-F, Abdelwahab MG. Interleukin-1β, tumor necrosis factor-α, and oxidative stress biomarkers in cows with acute Brucella abortus infection. Comp Clin Path. 2021;30(2):311-5.
  8. Priyanka, Shringi BN, Choudhary OP, Kashyap SK. Expression profiling of cytokine-related genes in Brucella abortus infected cattle. Biol Rhythm Res. 2021;52(5):654-65.