Abstrakt

Aim: Phagocytosing macrophages are involved in the induction of humoral immunity to corpuscular antigens. Recently, we demonstrated that B cell response to haptenated sheep red blood cells (SRBC) could be suppressed by extracellular vesicles (EVs) produced by suppressor T cells activated through intravenous administration of a high dose of syngeneic mouse red blood cells (sMRBC). However, the mechanism underlying the inhibitory effect of sMRBC-induced EVs on macrophages involved in activation of humoral immunity remained unclear. Thus, the current studies aimed at investigating the phagocytic and antigen-presenting activity of macrophages treated with sMRBC-induced EVs. Material/Methods: Mouse thioglycollate-induced peritoneal macrophages were treated with sMRBC-induced EVs and then pulsed with either native or fluorescein isothiocyanate-conjugated SRBC. Afterwards, macrophages were, respectively, administered intraperitoneally into naive recipients or subjected to flow cytometric analysis. The elicited humoral immune response was evaluated in plaque forming and haemagglutination assays. Results: Decreased number of B cells secreting SRBC-specific antibodies was shown in spleens of mouse recipients of SRBC-pulsed macrophages pretreated with sMRBC-induced EVs along with an increased ratio of IgM to IgG serum antibodies. Furthermore, pretreatment of macrophages with sMRBC-induced EVs reduced their phagocytic activity and expression of costimulatory molecules involved in antigen phagocytosis and presentation. Conclusions: Current research findings demonstrated the impaired ability of macrophages to activate B cells due to the action of sMRBC-induced EVs, which may play a role in suppressing self-reactive B cells. Thus, our results seem to have translational potential in development of therapeutic strategies to prevent the macrophage-induced humoral immunity against nonpathogenic antigens.

Przypisy

• 1. A-Gonzalez N., Quintana J.A., García-Silva S., Mazariegos M., Gonzálezde la Aleja A., Nicolás-Ávila J.A., Walter W., Adrover J.M., CrainiciucG., Kuchroo V.K., Rothlin C.V., Peinado H., Castrillo A., Ricote M.,Hidalgo A.: Phagocytosis imprints heterogeneity in tissue-residentmacrophages. J. Exp. Med., 2017; 214: 1281–1296
  Google Scholar
• 2. Bielinska A.U., Makidon P.E., Janczak K.W., Blanco L.P., SwansonB., Smith D.M., Pham T., Szabo Z., Kukowska-Latallo J.F., Baker J.R. Jr.:Distinct pathways of humoral and cellular immunity induced withthe mucosal administration of a nanoemulsion adjuvant. J. Immunol.,2014; 192: 2722–2733
  Google Scholar
• 3. Borriello F., Sethna M.P., Boyd S.D., Schweitzer A.N., Tivol E.A.,Jacoby D., Strom T.B., Simpson E.M., Freeman G.J., Sharpe A.H.: B7-1and B7-2 have overlapping, critical roles in immunoglobulin classswitching and germinal center formation. Immunity, 1997; 6: 303–313
  Google Scholar
• 4. Bryniarski K., Ptak W., Jayakumar A., Püllmann K., Caplan M.J.,Chairoungdua A., Lu J., Adams B.D., Sikora E., Nazimek K., MarquezS., Kleinstein S.H., Sangwung P., Iwakiri Y., Delgato E., et al.: Antigenspecific, antibody coated, exosome-like nanovesicles deliversuppressor T cell miRNA-150 to effector T cells to inhibit contactsensitivity. J. Allergy Clin. Immunol., 2013; 132: 170–181
  Google Scholar
• 5. Bryniarski K., Ptak W., Martin E., Nazimek K., Szczepanik M., SanakM., Askenase P.W.: Free extracellular miRNA functionally targetscells by transfecting exosomes from their companion cells. PLoSOne, 2015; 10: e0122991
  Google Scholar
• 6. Cho Y., Kwon D., Kang S.J.: The cooperative role of CD326+ andCD11b+ dendritic cell subsets for a hapten-induced Th2 differentiation.J. Immunol., 2017; 199: 3137-3146
  Google Scholar
• 7. Czajkowska B., Ptak M., Bobek M., Bryniarski K., Szczepanik M.:Different isoenzyme patterns of nonspecific esterases and the levelof IL-6 production as markers of macrophage functions. Folia Histochem.Cytobiol., 1995; 33: 111–115
  Google Scholar
• 8. Filipczak-Bryniarska I., Nazimek K., Nowak B., Kozlowski M.,Wąsik M., Bryniarski K.: In contrast to morphine, buprenorphineenhances macrophage-induced humoral immunity and, as oxycodone,slightly suppresses the effector phase of cell-mediated immuneresponse in mice. Int. Immunopharmacol., 2018; 54: 344–353
  Google Scholar
• 9. Filipczak-Bryniarska I., Nazimek K., Nowak B., Kozlowski M., WąsikM., Bryniarski K.: Data supporting the understanding of modulatoryfunction of opioid analgesics in mouse macrophage activity.Data Brief, 2017; 16: 950–954
  Google Scholar
• 10. Filipczak-Bryniarska I., Nowak B., Sikora E., Nazimek K., WorońJ., Wordliczek J., Bryniarski K.: The influence of opioids on thehumoral and cell-mediated immune responses in mice. The role ofmacrophages. Pharmacol. Rep., 2012; 64: 1200–1215
  Google Scholar
• 11. Fuentes-Duculan J., Suárez-Fariñas M., Zaba L.C., Nograles K.E.,Pierson K.C., Mitsui H., Pensabene C.A., Kzhyshkowska J., Krueger J.G.,Lowes M.A.: A subpopulation of CD163-positive macrophages is classicallyactivated in psoriasis. J. Invest. Dermatol., 2010; 130: 2412–2422
  Google Scholar
• 12. Ghosn E.E., Cassado A.A., Govoni G.R., Fukuhara T., Yang Y., MonackD.M., Bortoluci K.R., Almeida S.R., Herzenberg L.A., Herzenberg L.A.:Two physically, functionally, and developmentally distinct peritonealmacrophage subsets. Proc. Natl. Acad. Sci. USA, 2010; 107: 2568–2573
  Google Scholar
• 13. Groot Kormelink T., Mol S., de Jong E.C., Wauben M.H.: The roleof extracellular vesicles when innate meets adaptive. Semin. Immunopathol.,2018; 40: 439–452
  Google Scholar
• 14. Ho M.K., Springer T.A.: Tissue distribution, structural characterization,and biosynthesis of Mac-3, a macrophage surface glycoprotein exhibitingmolecular weight heterogeneity. J. Biol. Chem., 1983; 258: 636–642
  Google Scholar
• 15. Hultqvist M., Olofsson P., Holmberg J., Bäckström B.T., TordssonJ., Holmdahl R.: Enhanced autoimmunity, arthritis, and encephalomyelitisin mice with a reduced oxidative burst due to amutation in the Ncf1 gene. Proc. Natl. Acad. Sci. USA, 2004; 101:12646–12651
  Google Scholar
• 16. Kraaij M.D., Savage N.D., van der Kooij S.W., Koekkoek K., WangJ., van den Berg J.M., Ottenhoff T.H., Kuijpers T.W., Holmdahl R., vanKooten C., Gelderman K.A.: Induction of regulatory T cells by macrophagesis dependent on production of reactive oxygen species.Proc. Natl. Acad. Sci. USA, 2010; 107: 17686–17691
  Google Scholar
• 17. Lin H.H., Faunce D.E., Stacey M., Terajewicz A., Nakamura T.,Zhang-Hoover J., Kerley M., Mucenski M.L., Gordon S., Stein-StreileinJ.: The macrophage F4/80 receptor is required for the induction ofantigen-specific efferent regulatory T cells in peripheral tolerance.J. Exp. Med., 2005; 201: 1615–1625
  Google Scholar
• 18. Liu X., Fu B., Chen D., Hong Q., Cui J., Li J., Bai X., Chen X.: miR- 184 and miR-150 promote renal glomerular mesangial cell agingby targeting Rab1a and Rab31. Exp. Cell. Res., 2015; 336: 192–203
  Google Scholar
• 19. Miwa H., Kanno H., Munakata S., Akano Y., Taniwaki M., AozasaK.: Induction of chromosomal aberrations and growth-transformationof lymphoblastoid cell lines by inhibition of reactive oxygenspecies-induced apoptosis with interleukin-6. Lab. Invest., 2000;80: 725–734
  Google Scholar
• 20. Nazimek K., Askenase P.W., Bryniarski K.: Antibody light chainsdictate the specificity of contact hypersensitivity effector cellsuppression mediated by exosomes. Int. J. Mol. Sci., 2018; 19: E2656
  Google Scholar
• 21. Nazimek K., Bryniarski K.: The biological activity of macrophagesin health and disease. Postępy Hig. Med. Dośw., 2012; 66: 507–520
  Google Scholar
• 22. Nazimek K., Bryniarski K., Askenase P.W.: Functions of exosomesand microbial extracellular vesicles in allergy and contact and delayed-type hypersensitivity. Int. Arch. Allergy Immunol., 2016; 171: 1–26
  Google Scholar
• 23. Nazimek K., Kozlowski M., Bryniarski P., Strobel S., Bryk A.,Myszka M., Tyszka A., Kuszmiersz P., Nowakowski J., Filipczak-BryniarskaI.: Repeatedly administered antidepressant drugs modulatehumoral and cellular immune response in mice through action onmacrophages. Exp. Biol. Med., 2016; 241: 1540–1550
  Google Scholar
• 24. Nazimek K., Nowak B., Marcinkiewicz J., Ptak M., Ptak W., BryniarskiK.: Enhanced generation of reactive oxygen intermediatesby suppressor T cell-derived exosome-treated macrophages. FoliaMed. Cracov., 2014; 54: 37–52
  Google Scholar
• 25. Nazimek K., Ptak W., Nowak B., Ptak M., Askenase P.W., BryniarskiK.: Macrophages play an essential role in antigen-specific immunesuppression mediated by T CD8+ cell-derived exosomes. Immunology,2015; 146: 23–32
  Google Scholar
• 26. Ptak W., Nazimek K., Askenase P.W., Bryniarski K.: From mysterioussupernatant entity to miRNA-150 in antigen-specific exosomes:a history of hapten-specific T suppressor factor. Arch. Immunol.Ther. Exp., 2015; 63: 345–356
  Google Scholar
• 27. Tripathi P., Hildeman D.: Sensitization of T cells to apoptosis – arole for ROS? Apoptosis, 2004; 9: 515–523
  Google Scholar
• 28. Waddell L.A., Lefevre L., Bush S.J., Raper A., Young R., LisowskiZ.M., McCulloch M.E.B., Muriuki C., Sauter K.A., Clark E.L., IrvineK.M., Pridans C., Hope J.C., Hume D.A.: ADGRE1 (EMR1, F4/80) is arapidly-evolving gene expressed in mammalian monocyte-macrophages.Front. Immunol., 2018; 9: 2246
  Google Scholar
• 29. Xiao C., Calado D.P., Galler G., Thai T.H., Patterson H.C., Wang J., RajewskyN., Bender T.P., Rajewsky K.: MiR-150 controls B cell differentiationby targeting the transcription factor c-Myb. Cell, 2007; 131: 146–159
  Google Scholar
• 30. Ying W., Tseng A., Chang R.C., Wang H., Lin Y.L., Kanameni S.,Brehm T., Morin A., Jones B., Splawn T., Criscitiello M., Golding M.C.,Bazer F.W., Safe S., Zhou B.: miR-150 regulates obesity-associated insulinresistance by controlling B cell functions. Sci. Rep., 2016; 6: 20176
  Google Scholar
• 31. Zhou B., Wang S., Mayr C., Bartel D.P., Lodish H.F.: miR-150, amicroRNA expressed in mature B and T cells, blocks early B cell developmentwhen expressed prematurely. Proc. Natl. Acad. Sci. USA,2007; 104: 7080–7085
  Google Scholar

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