CHANGES IN THE EXPOSURE OF CD11B ON THE SURFACE OF GRANULOCYTES, AFTER ACTIVATION OF TOLL-LIKE RECEPTORS IN CHILDREN WITH RECURRENT INFECTIONS

D. V. Osypchuk, O. V. Rabosh


DOI: http://dx.doi.org/10.30970/sbi.1001.468

Abstract


The effect of activation of Toll-like receptors (TLR) on presentation of CD11b adhesion molecule at the granulocytes surface in children of different age with recurrent infections was investigated. Stimulation of TLR2, TLR4, TLR7/TLR8 by agonists led to a significant increase of the content of integrin CD11b in the granulocytes cytoplasmic membrane. The amount of CD11b after stimulation of TLR7/8, was lower in groups of children with recurrent infections, compared with matched-age control groups. The amount of integrin CD11b on granulocytes surface, following activation TLR, did not differ statistically between the studied and control groups of different ages. In addition, we analyzed the ligand-dependent content of CD11b in granulocytes surface membrane of each group. Thus, in the control groups, amount of CD11b did not differ statistically after incubation of blood cells with agonists of TLRs (LPS, R848 and PGN). Conversely, in groups of children with recurrent infections, levels of induced CD11b production were statistically distinctive depends on ligands and the lowest content of CD11b was obtained after incubation of blood cells with R848. Thus, exploring the influence of TLR activation on the amount of integrin CD11b on the granulocyte’s surface showed that the growth rate of CD11b after activation, independent of age. Groups of children with recurrent infections showed significantly lower amount of CD11b on granulocytes after activation of TLR7/8, compared with age-matched control groups. Such a decreased presentation of adhesion molecules at gra­nu­locyte’s surface in response to TLR7/8 stimulation by R848 can lead to preventing migration of granulocytes to the infection site and promote an increased sensitivity to viral infections and bacterial complications.


Keywords


Toll-like receptors (TLR), granulocytes, CD11b adhesion molecular

Full Text:

PDF

References


1. Bouma G., Doffinger R., Patel S.Y. Impaired neutrophil migration and phagocytosis in IRAK-4 deficiency. Br. J. Haematol, 2009; 4(7): 153-6.
https://doi.org/10.1111/j.1365-2141.2009.07838.x
PMid:19663824

2. Dziarski R., Gupta D. Staphylococcus aureus Peptidoglycan Is a Toll-Like Receptor 2 Activator: a Reevaluation. Infect. Immun, 2005; 73(8): 5212-6.
https://doi.org/10.1128/IAI.73.8.5212-5216.2005
PMid:16041042 PMCid:PMC1201261

3. Fong O.N., Chan K.Y., Leung K.T. Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan. J. Leukoc. Biol, 2014; 95(1): 169-78.
https://doi.org/10.1189/jlb.0413219
PMid:23986550

4. Hattermann K., Picard S., Borgeat M. et al. The Toll-like receptor 7/8-ligand resiquimod (R-848) primes human neutrophils for leukotriene B4, prostaglandin E2 and platelet-activating factor biosynthesis. FASEB J, 2007; 21(7): 1575-85.
https://doi.org/10.1096/fj.06-7457com
PMid:17264163

5. Hayashi F., Means T.K., Luster A.D. Toll-like receptors stimulate human neutrophil function. Blood, 2003; 102: 2660-69.
https://doi.org/10.1182/blood-2003-04-1078
PMid:12829592

6. Heine H. TLRs, NLRs and RLRs: Innate sensors and their impact on allergic diseases. Immunol. Lett, 2011; 30(139): 14-24.
https://doi.org/10.1016/j.imlet.2011.04.010
PMid:21554901

7. Heltzer M.L., Coffin S.E., Maurer K. et al. Immune dysregulation in severe influenza. J. Leukoc. Biol, 2009; 85(6):1036-43.
https://doi.org/10.1189/jlb.1108710
PMid:19276177 PMCid:PMC2698588

8. Jenne C.N., Wong C.H., Zemp F.J. et al. Neutrophils Recruited to Sites of Infection Protect from Virus Challenge by Releasing Neutrophil Extracellular Traps. Cell. Host. Microbe, 2013; 13(2): 169-80.
https://doi.org/10.1016/j.chom.2013.01.005
PMid:23414757

9. Kobayashi S.D., Voyich J.M., Burlak C. et al. Neutrophils in the innate immune response.Arch. Immunol. Ther. Exp, 2005; 53:505-17.

10. Kumar V., Sharma A. Neutrophils: Cinderella of innate immune system. Int. Immunopharmacol, 2010; 10(11): 1325-34.
https://doi.org/10.1016/j.intimp.2010.08.012
PMid:20828640

11. Ku C.L., von Bernuth H.,Picard C. et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J. Exp. Med, 2007; 204: 2407-22.

12. Langer M., Malykhin A., Maeda K. et al. Bacillus anthracis Peptidoglycan Stimulates an Inflammatory Response in Monocytes through the p38 Mitogen-Activated Protein Kinase Pathway. PLoSONE, 2008; 3(11): e3706.
https://doi.org/10.1371/journal.pone.0003706
PMid:19002259 PMCid:PMC2577892

13. Mallia P., Message S., Contoli M. et al.Neutrophil adhesion molecules in experimental rhinovirus infection in COPD. Respir. Res, 2013; 14: P. 72.
https://doi.org/10.1186/1465-9921-14-72
PMid:23834268 PMCid:PMC3726453

14. Medzhitov R. Toll-like receptors and innate immunity. Immunology, 2001; 1: 135-145.
https://doi.org/10.1038/35100529
PMid:11905821

15. Tang F.S., Van Ly D., Spann K. Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma. Respirology, 2016; 21(1): 172-9.
https://doi.org/10.1111/resp.12657
PMid:26477783 PMCid:PMC5324549

16. Springer T. A. Adhesion receptors of the immune system. Nature,1990; 346: 425-434.
https://doi.org/10.1038/346425a0
PMid:1974032


Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 Studia biologica

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