The role of endogenous antibacterial peptides in pneumonia occurrence among children of young age

G.O. Lezhenko, A.E. Abaturov, O.E. Pashkova, H.V. Kraynya

Abstract


The comprehensive examination included 204 children with community-acquired pneumonia aged 2 months to 3 years. It was found that in young children with community-acquired pneumonia, the main etiologic factor is bacteria Streptococcus pneumoniae (36.8 %). The content of endogenous antimicrobial peptides was identified in the serum of 20 young children with pneumonia and in 17 children in the control group. It is proved that the development of pneumonia in young children occurs on the background of the reduction in the blood serum levels of β1-defensin and cathelicidin LL-37. The lowest values of LL-37 were identified in children with pneumonia caused by Streptococcus pneumoniae. The analysis of the content of vitamin D metabolites in the serum showed that in children with pneumonia, concentration of 25-hydroxyvitamin D was 1.4 times lower compared with healthy children (р < 0.05). Established deficiency of vitamin D metabolites in young children with community-acquired pneumonia serves as an important pathogenetic factor for cathelicidin LL-37 deficiency in the blood serum, which was confirmed by 3.7-times decrease in the percentage of LL-37 compared with vitamin D metabolites in this cohort of patients.

Keywords


community-acquired pneumonia; β1-defensin; cathelicidin LL-37; 25-hydroxyvitamin D; young children

Full Text:

PDF

References


McIntosh K. Community-acquired pneumonia in children. New England Journal ofMedicine. 2002;346(6):429-37. doi: 10.1056/NEJMra011994.

World Health Organization (WHO). Pneumonia fact sheet. Fact sheet 331. Reviewed September 2016. Available at: www.who.int/mediacentre/factsheets/fs331/en/.

Wu Rui-Qing, Dun-Fang Zhang, Eric Tu, et al. The mucosal immune system in the oral cavity — an orchestra of T cell diversity. Int J Oral Sci. 2014 Sept;6(3):125-32. PMC4170154. doi:10.1038/ijos.2014.48.

Tyrnova EV, Aleshina GM, Yanov YuK, Kokryakov VN. Ekspressiya genov β -defensinov-1 i -2 i katelitsidina LL-37 v slizistoy dykhatelnykh putey. Otsenka ekspressii genov beta-defensinov-1 i -2 cheloveka i katelitsidina LL-37 v slizistoy obolochke verkhnikh dykhatelnykh putey [Expression of the β-defensin-1 and -2 and catelicidin LL-37 in the respiratory mucosa. Estimation of human beta-defensins-1, 2 and cathelicidin LL-37 genes expression in the upper airway mucosa]. Tsitokiny i vospaleniye. 2014;13( 2):89-95. (in Russian).

Aleshina GM, Kokryakov VN, Shamova OV. Covremennaya kontseptsiya ob antimikrobnyih peptidah kak molekulyarnyih faktorah immuniteta [Modern concept of antimicrobial peptides as molecular factors of immunity]. Meditsinskiy akademicheskiy zhurnal. 2010;4:149-60. (in Russian).

Hiemstra PS, Amatngalim GD, van der Does AM, Taube C. Antimicrobial Peptides and Innate Lung Defenses: Role in Infectious and Noninfectious Lung Diseases and Therapeutic Applications. Chest. 2016;149(2):545-51. PMID: 26502035.   doi:10.1378/chest.15-1353.

Miroshnichenko YuA, Shestopalov AV, Smolyaninova LP. Rol faktorov vrozhdennogo immuniteta slizistoy obolochki reproduktivnogo trakta [The role of factors of congenital immunity of the mucous membrane of the reproductive tract]. Zhurnal fundamentalnoy meditsinyi i biologii. 2013;1:S11.

Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389-95. PMID: 11807545. doi:10.1038/415389a.

Zaiou М, Nizet V, Gallo RL. Antimicrobial and Protease Inhibitory Functions of the Human Cathelicidin (hCAP18/LL-37) Prosequence. The Journal of Investigative Dermatology. 2003;120(5):810–6. PMID: 12713586. doi:1523-1747.2003.12132.x.

Hansdottir S, Monick MM, Hinde SL. Respiratory epithelial cells convertinactive vitamin D toits active form: potential effects on hostdefense. J Immunol. 2008 Nov 15;181(10):7090-9. PMID: 18981129. doi: 10.4049/jimmunol.181.10.7090.

Zaharova IN, Yablochkova SV, Dmitrieva YuA. Izvestnyie i neizvestnyie effekty ivitamina D [Well-known and Indeterminate Effects of Vitamin D]. Voprosyi sovremennoy pediatrii. 2013;2:20-25. doi: 10.15690/vsp.v12i2.616 (in Russian).

Gorgoni B, MaritanoD, Marthyn P. C/EBP beta gene inactivation causes both impaired and enhanced gene expression and inverse regulation of IL‑12 p40 and p35 mRNAs in macrophages. Journal of Immunology. 2002;168(8):4055-62. PMID: 11937564. doi: 10.4049/jimmunol.168.8.4055.

Yim S, Dhawan P, Ragunath C, et al. Induction of cathelicidin in normaland CF bronchial epithelial cells by 1,25 dihydroxy Vitamin D3. Journal of Cystic Fibrosis. 2007 Nov 30;6(6):403-10. PMID: 17467345. doi: 10.1016/j.jcf.2007.03.003.

Belderbos ME, Houben ML, Wilbrink B. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011;127(6):1513-20. PMID: 21555499. doi: 10.1542/peds.2010-3054.

Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr. 2004 Apr;58(4):563-7. PMID: 15042122. doi: 10.1038/sj.ejcn.1601845.

Pikuza OI, Samorodnova EA. Sovremennyie osobennosti vnebolnichnyih pnevmoniy u detey rannego vozrasta [Contemporary pecularities of community-acquired pneumonia in children of tender age]. Prakticheskaya meditsina. 2013;6(75):35-41. (in Russian).

Charlson ES, Bittinger K, Haas AR. Topographical Continuity of Bacterial Populations in the Healthy Human Respiratory Tract. Amer J Respir And Crit Care Med. 2011;184(8):957-63. PMID: 21680950. doi:10.1164/rccm.201104-0655OC.

Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005 Mar;3(3):238-50. PMID: 15703760. doi:10.1038/nrmicro1098.

Burton MF, Steel PG. The chemistry and biology of LL-37. Nat Prod Rep. 2009;26:1572–84. PMID: 19936387. doi:10.1039/b912533g.

Habets MG, Rozen DE, Brockhurst MA. Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition. Proc Biol Sci. 2012 Sep 22;279(1743):3803-11. PMID: 22764166. doi: 10.1098/rspb.2012.1118.

Abaturov AE., Gerasimenko ON., Vyisochina IL., Zavgorodnyaya NYu. Defenzinyi i defenzin-zavisimyie zabolevaniya [Defensins and defensin-dependent diseases]. Odessa: VMV; 2011. 264p. (in Russian).

Doss M, White MR, Tecle T, Hartshorn KL. Human defensins and LL-37 in mucosal immunity. Journal of leukocyte biology. 2010 Jan;87(1):79-92. PMID: 19808939. doi: 10.1189/jlb.0609382.

De Medeiros LN, Angeli R, Sarzedas CG. Backbone dynamics of the antifungal Psd1 pea defensin and its correlation with membrane interaction by NMR spectroscopy. Biochim Biophys Acta. 2010 Feb;1798(2):105-113. PMID: 19632194. doi: 10.1016/j.bbamem.2009.07.013.

Shenkarev ZO, Gizatullina AK, Finkina EI. Heterologous expression and solution structure of defensin from lentil Lens culinaris. Biochem Biophys Res Commun. 2014;451:252-7. doi: 10.1016/j.bbrc.2014.07.104.

Schroeder BO, Wu Z, Nuding S, et al. Reduction of disulphide bonds un masks potent antimicrobial activity of human β-defensin 1. Nature. 2011 Jan 20;469(7330):419-23. PMID: 21248850.  doi: 10.1038/nature09674.

Raschig J, Mailänder-Sanchez D, Berscheid A, et al. Ubiquitously expressed Human Beta Defensin 1 (hBD1) forms bacteria-entrapping nets in a redox dependent mode of action. PloS pathogens. 2017;13(3):S1006261. doi: 10.1371/journal.ppat.1006261.

Nakayama K, Jia YX, Hirai H. Acid stimulation reduces bactericidal activity of surface liquid in cultured human air way epithelial cells. American journal of respiratory cell and molecular biology. 2002;26(1):105-113. PMID: 11751210. doi: 10.1165/ajrcmb.26.1.4425.

Shabalov NP. Pnevmonii u detey rannego vozrasta [Pneumonia in young children]. Lechaschiy vrach. 2003;2:16-22. (in Russian).

Wan M, vander Does AM, Tang X, et al. Antimicrobial peptide LL-37 promotes bacterial phagocytosis by human macrophages. J Leukoc Biol. 2014 Jun;95(6):971-81. PMID: 24550523. doi: 10.1189/jlb.0513304.

Felgentreff K, Beisswenger C, Griese M, et al. The antimicrobial peptide cathelicidin interacts with air way mucus. Peptides. 2006 Dec;27(12):3100-06. PMID: 16963160. doi: 10.1016/j.peptides.2006.07.018.

Gryllos I, Tran-Winkler HJ, Cheng MF, et al. Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc Natl Acad Sci U. S. A. 2008;105(43):16755-60. PMID: 18936485. doi: 10.1073/pnas.0803815105.

Velarde JJ, Ashbaugh M, Wessels MR. The human antimicrobial peptide LL-37 binds directly to CsrS, a sensor histidine kinase of group A Streptococcus, to active at expression of virulence factors. J Biol Chem. 2014 Dec 26;289(52):36315-24. PMID: 25378408. doi: 10.1074/jbc.M114.605394.

Wang G. Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J. Biol. Chem. 2008;283:32637–43. PMID: 18818205. doi: 10.1074/jbc.M805533200.

Epand RF, Wang G, Berno B, Epand RM. Lipid segregation explains selective toxicity of a series of fragments derived from the human cathelicidin LL-37. Antimicrob Agents Chemother. 2009;53:3705-14. doi: 10.1128/AAC.00321-09.

Wang G, Epand RF, Mishra B, et al. Decoding the functional roles of cationic side chains of the major antimicrobial region of human cathelicidin LL-37. Antimicrob Agents Chemother. 2012;56(2):845-56. doi: 10.1128/AAC.05637-11.

Abou Alaiwa MH, Reznikov LR, Gansemer ND, et al. pH modulates the activity and synergis mofthe airway surface liquid antimicrobials beta-defensin-3 and LL-37. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52): 18703-8. PMID: 25512526. doi: 10.1073/pnas.1422091112.

Johansson J, Gudmundsson GH, Rottenberg ME. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. J Biol Chem. 1998 Feb 6;273(6):3718-24. PMID: 9452503. doi: 10.1074/jbc.273.6.3718.

Singh D, Vaughan R, Kao CC. LL-37 peptide enhancement of signal transduction by toll-like receptor 3 is regulated by pH: identification of a peptide antagonist of LL-37. J Biol Chem. 2014 Oct 3;289(40):27614–24. PMID: 25092290. doi: 10.1074/jbc.M114.582973.

Yamasaki K, Schauber J, Coda A, et al. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB Journal. 2006 Oct;20(12):2068-80. PMID:17012259. doi: 10.1096/fj.06-6075com.

Zaharova IN. Vitamin D: neizvestnoe ob izvestnom [Vitamin D: unknown about the known]. Rossiyskiy meditsinskiy zhurnal. 2015;3:S118. (in Russian).

Zaharova IN, Dmitrieva YuA, Yablochkova SV. Modern view on the metabolism and physiological effects of vitamin D in the human body. Vestnik Almatinskogo gosudarstvennogo instituta usovershenstvovanija vrachej. 2013;2:27-31. (in Russian).

Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24;311(5768):1770-3. PMID: 16497887. doi: 10.1126/science.1123933.

Leow L, Simpson T, Cursons R, Karalus N, Hancox RJ. Vitamin D, innate immunity and outcomes in community acquired pneumonia. Respirology. 2011 May;16(4):611-6. PMID: 21244571. doi: 10.1111/j.1440-1843.2011.01924.x.

Laaksi I, Ruohola JP, Tuohimaa P. An association of serum vitamin D concentrations < 40 nmol/l with acute respiratory tract infection in young Finnishmen. Am J Clin Nutr. 2007 Sep;86(3):714-7. PMID: 17823437. doi: 10.3390/nu5072502.

Karatekin G, Kaya A, Salihoglu O. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur J Clin Nutr. 2009 Apr;63(4):473-7. PMID: 18030309. doi: 10.1038/sj.ejcn.1602960.

De Boer IH, Vitamin D and glucose metabolism in chronic kidney disease. Current opinion in nephrology and hypertension. 2008;17(6):566. doi: 10.1097/MNH.0b013e32830fe377.

Lee SW, Russell J, Avioli LV. 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol: conversion impaired by systemic metabolic acidosis. Science. 1977 Mar 11;195(4282): 994-6. PMID: 841324. doi: 10.1126/science.841324.

Kawashima H, Kraut JA, Kurokawa K. Metabolic acidosis suppresses 25-hydroxyvitamin in D3-1alpha-hydroxylase in the rat kidney. Distinct site and mechanism of action. J Clin Invest. 1982 Jul;70(1):135-40. PMID: 6282936. doi: 10.1172/JCI110586.

Chan YL, Sardie E, Mason RS, Posen S. The effect of metabolic acidosis on vitamin D metabolism and bone histology in uremic rats. Calcif Tissue Int. 1985 Mar;37:158-64. PMID: 3924372. doi: 10.1007/BF02554835.

Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007 Aug;179(4):2060-3. PMID: 17675463. doi: 10.4049/jimmunol.179.4.2060.




DOI: https://doi.org/10.22141/2224-0551.12.2.2017.99762

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

 

© Publishing House Zaslavsky, 1997-2017

 

 Яндекс.МетрикаSeo анализ сайта Рейтинг@Mail.ru