TY - JOUR

T1 - Influence of caudovirales phages on humoral immunity inmice

AU - Chechushkov, Anton

AU - Kozlova, Yuliya

AU - Baykov, Ivan

AU - Morozova, Vera

AU - Kravchuk, Bogdana

AU - Ushakova, Tatyana

AU - Bardasheva, Alevtina

AU - Zelentsova, Ekaterina

AU - Al Allaf, Lina

AU - Tikunov, Artem

AU - Vlassov, Valentin

AU - Tikunova, Nina

N1 - Funding Information: This study was supported by Russian Scientific Foundation, research project No. 19-75- 00065. Collection of EMTC ICBFM SB RAS was supported by Russian State funded budget project of ICBFM SB RAS No. 121031300043-8. Publisher Copyright: © 2021 by the authors. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - Bacteriophages are promising antibacterial agents. Although they have been recognized as bacterial viruses and are considered to be non-interacting with eukaryotic cells, there is growing evidence that phages may have a significant impact on the immune system via interactions with macrophages, neutrophils, and T-cell polarization. In this study, the influence of phages of podovirus, siphovirus, and myovirus morphotypes on humoral immunity of CD-1 mice was investigated. In addition, tissue distribution of the phages was tested in these mice. No common patterns were found either in the distribution of phages in mice or in changes in the levels of cytokines in the sera of mice once injected with phages. Importantly, pre-existing IgM-class antibodies directed against capsid proteins of phages with myovirus and siphovirus morphotypes were identified in mice before immunization. After triple immunization of CD1-mice with phages without any adjuvant, levels of anti-phage serum polyclonal IgG antibodies increased. Immunogenic phage proteins recognized by IgM and/or IgG antibodies were identified usingWestern blot analysis and mass spectrometry. In addition, mice serum collected after immunization demonstrated neutralizing properties, leading to a substantial decrease in infectivity of investigated phages with myovirus and siphovirus morphotypes. Moreover, serum samples collected before administration of these phages exhibited some ability to reduce the phage infectivity. Furthermore, Proteus phage PM16 with podovirus morphotype did not elicit IgM or IgG antibodies in immunized mice, and no neutralizing activities against PM16 were revealed in mouse serum samples before and after immunization.

AB - Bacteriophages are promising antibacterial agents. Although they have been recognized as bacterial viruses and are considered to be non-interacting with eukaryotic cells, there is growing evidence that phages may have a significant impact on the immune system via interactions with macrophages, neutrophils, and T-cell polarization. In this study, the influence of phages of podovirus, siphovirus, and myovirus morphotypes on humoral immunity of CD-1 mice was investigated. In addition, tissue distribution of the phages was tested in these mice. No common patterns were found either in the distribution of phages in mice or in changes in the levels of cytokines in the sera of mice once injected with phages. Importantly, pre-existing IgM-class antibodies directed against capsid proteins of phages with myovirus and siphovirus morphotypes were identified in mice before immunization. After triple immunization of CD1-mice with phages without any adjuvant, levels of anti-phage serum polyclonal IgG antibodies increased. Immunogenic phage proteins recognized by IgM and/or IgG antibodies were identified usingWestern blot analysis and mass spectrometry. In addition, mice serum collected after immunization demonstrated neutralizing properties, leading to a substantial decrease in infectivity of investigated phages with myovirus and siphovirus morphotypes. Moreover, serum samples collected before administration of these phages exhibited some ability to reduce the phage infectivity. Furthermore, Proteus phage PM16 with podovirus morphotype did not elicit IgM or IgG antibodies in immunized mice, and no neutralizing activities against PM16 were revealed in mouse serum samples before and after immunization.

KW - Antibodies

KW - Bacteriophage

KW - Future medicine

KW - Humoral immunity

KW - IgG

KW - IgM

KW - Immunogenicity

KW - Neutralization

KW - Phage therapy

UR - http://www.scopus.com/inward/record.url?scp=85109510194&partnerID=8YFLogxK

U2 - 10.3390/v13071241

DO - 10.3390/v13071241

M3 - Article

C2 - 34206836

AN - SCOPUS:85109510194

VL - 13

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 7

M1 - 1241

ER -