Neutrophil, TLR2, and TLR4 expression in newborns at risk of sepsis

Main Article Content

Ari Yunanto
Agustina Tri Endharti
Aris Widodo

Abstract

Background There is increasing evidence that toll-like receptors (TLR) play a key role in the mediation of systemic responses to invading pathogens during sepsis. Saliva is an important body fluid for detecting physiological and pathological conditions of the human body. Neutrophils are participants in the acute response against pathogens in many tissues, and their influx into the oral cavity may occur at any time.
Objective To compare mean neutrophils and the expression of TLR2 and TLR4 in saliva and blood of newborns at risk for sepsis to those of healthy newborns.
Methods This cross-sectional study was conducted from July to December 2011 in the Division of Neonatology, Department of Child Health, Ulin General Hospital, Lambung Mangkurat University Medical School, Banjarmasin. Case subjects were newborns with sepsis risk factors (30 infants), while 30 healthy infants were in the control group. Saliva and blood specimen examinations were performed in the Biomedical Laboratory of Brawijaya University Medical School, Malang. We used T-test for statistical analyses.
Results From saliva specimens, mean neutrophils were significantly higher in the case group than in the control group [14.43 (SD 12.21) % vs. 5.63 (SD 6.78) %, respectively, (P=0.021)]. In addition, mean TLR2 and mean TLR4 saliva levels were significantly higher in the case group than in the control group [TLR2: 64.97 (SD 26.42) % vs. 40.06 (SD 6.23) %, respectively, (P=0.011); TLR4: 1.5 (SD 1.61) % vs. 0.57 (SD 0.53) %, respectively, (P=0.044)]. From blood specimens, mean neutrophils were also significantly higher in the case group than in the control group [1.09 (SD 0.61)% vs. 0.21 (SD 0.09)%, respectively, (P=0.000)]. Similarly, mean blood TLR2 and TLR4 levels were significantly higher in the case group than in the control group [TLR2: 92.51 (SD 5.51) % vs. 81.74 (SD 11.79) %, respectively, (P=0.003); TLR4: 0.71 (SD 1.42) % vs. 0.12 (SD 0.06) %, respectively, (P=0.000)].
Conclusion There are significant increases in neutrophils, as well as neutrophil expression of TLR2 and TLR4 in the saliva and blood from newborns with sepsis risk factors compared to those of healthy newborns. [Paediatr Indones. 2013;53:132-7.]

Article Details

How to Cite
1.
Yunanto A, Endharti A, Widodo A. Neutrophil, TLR2, and TLR4 expression in newborns at risk of sepsis. PI [Internet]. 30Jun.2013 [cited 13Aug.2020];53(3):132-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/377
Section
Articles
Received 2016-08-30
Accepted 2016-08-30
Published 2013-06-30

References

1. Bizzaro JM, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of sepsis at Yale: 1928 – 2003. Pediatrics. 2005;116:595-602.
2. Macdonald J, Galley HF, Webster NR. Oxidative stress and gene expression in sepsis. Br J Anaesth. 2003;90:221-32.
3. Russell JA. Management of sepsis. N Engl J Med. 2006;355:1699-713.
4. Quinn MT, Gauss KA. Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol. 2004;76:760-81.
5. Nishiya T, De Franco AL. Ligand-regulated chimeric receptor approach reveals distinctive subcellular localization and signaling properties of the toll-like receptors. J Biol Chem. 2004;270:19008-17.
6. Cinei S, Opal MS. Molecular biology of inflammation and sepsis. Crit Care Med. 2009;37:291-304.
7. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1:135-45.
8. Dauphinee SM, Karsan A. Lipopolysaccharide signaling in endothelial cells. Lab Invest. 2006;86:9-22.
9. Werts C, Tapping RI, Mathison JC, Chuang TH, Kravchenko V, Saint Girons I, et al. Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat Immunol. 2001;2:346-52.
10. Smith MF, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, et al. Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-κB activation and chemokine expression by epithelial cells. J Biol Chem. 2003;278:32552-60.
11. Hashimoto M, Asai Y, Ogawa T. Separation and structural analysis of lipoprotein in a lipopolysaccharide preparation from Porphyromonas gingivalis. Int Immunol. 2004;16:1431-7.
12. Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, et al. The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA. 2005;102:9577–82.
13. Gao B, Tsan MF. Endotoxin contamination in recombinant human heat shock protein 70 (hsp70) preparation is responsible for the induction of tumor necrosis factor α release by murine macrophages. J Biol Chem. 2003;278:174-9.
14. Kaufman E, Lamster IB. The diagnostic applications of saliva: a review. Crit Rev Oral Biol Med. 2002;13:197-212.
15. Aminullah A, Gatot D, Kosim S. Penatalaksanaan sepsis neonatorum. Jakarta: Health Technology Assessment Indonesia & Indonesia Ministry of Health. 2007;33-4.
16. Urlichs R, Speer CP. Neutrophil function in preterm and term infant. Neoreview. 2004;5:e417-9.
17. Anwer SK, Mustafa S. Rapid identification of neonatal sepsis. J Pak Med Assoc. 2000;50:94-8.
18. Bhandari V, Wang C, Rinder C, Rinder H. Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic marker. Pediatrics. 2008;121:129-34.
19. Viemann D, Dubbel G, Schleifenbaum S, Harms E, Sorg C, Roth J. Expression of Toll-like receptor in neonatal sepsis. Pediatr Res. 2005;58:654-9.
20. Halfhide CP, Brearey SP, Flanagan BF, Hunt JA, Howarth D, Cummerson J, et al. Neutrophil TLR4 expression is reduced in the airways of infants with severe bronchiolitis. Thorax. 2009;64:798-805.
21. Samaranayake N. Is saliva the magic diagnostic fluid we were waiting for? Saudi Dental J. 2008;20:3.
22. Lima DP, Diniz DG, Moimaz SA, Sumida DH, Okamoto AC. Saliva: reflection of the body. Intl J Infect Dis. 2010;14:e184-8.
23. Kumar PS, Kumar S, Savadi RC, John J. Nanodentistry: a paradigm shift - from fiction to reality. J Indian Prosthodont Soc. 2011;11:1-6.
24. Ogawa K, Furukawa S, Fujita S, Mitobe J, Kawarai T, Narisawa R, et al. Inhibition of Streptococcus mutans biofilm formation by Streptococcus salivarius FruA. Appl Environ Microbiol. 2011;77:1572-80.
25. Markopoulos AK, Michailidou EZ, Tzimagiorgis G. Salivary markers for oral cancer detection. Open Dent J. 2010;4:172-8.
26. Wong DT. Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc. 2006;137:313-21.
27. Pink R, Simek J, Vondrokova J, Faber E, Michl P, Pazdera J, et al. Saliva is a diagnostic medium. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009;152:103-10.
28. Gasparoto TH, Vieira NA, Porto VC, Campanelli AP, Lara VS. Ageing exacerbates damage of systemic and salivary neutrophils from patients presenting Candida-related denture stomatitis. Immun Ageing. 2009;6:3.
29. William DL, Ha T, Li C, Kalbfleisch JH, Schweitzer J, Vogt W, et al. Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality. Crit Care Med. 2003;31:1808-18.
30. Tsujimoto H, Ono S, Efron PA, Scumpia PO, Moldawer LL, Mochizuki H. Role of Toll-like receptors in the development of sepsis. Shock. 2008;29:315-21