The Effect of Lactic Acid Bacteria and Bifidobacteria on the Number of Natural Killer Cells in Normal Conditions and in Cases of Intravaginal Staphylococcosis in Mice




Lactic acid bacteria, Bifidobacteria, Natural killer cells, Spleen, Intravaginal staphylococcosis, Mice


Background. Development of new immunobiotics based on commensal nonpathogenic probiotic bacteria such as lactic acid bacteria and bifidobacteria with antibacterial and immunomodulatory effects is an important area of modern biotechnology.

Оbjective. The aim of this study was to determine the effect of Lactobacillus acidophilus IMV B-7279, L. casei IMV B-7280, L. delbrueckii subsp. bulgaricus ІМV В-7281, Bifidobacterium animalis VKL and B. animalis VKB (individually) or their different compositions on the number of natural killer cells (NKC) in the spleen of BALB/c mice at normal conditions and in the case of the experimental intravaginal staphylococcosis.

Methods. The number of NKC in the spleen was studied using monoclonal phycoerythrin-conjugated antibodies against NKC antigens (MACS, Miltenyi Biotec, Germany). Calculations of NKC as well as analysis of the results were performed using flow cytometry method on a FACStar Plus cytofluorometer.

Results. It is shown that the number of NKC in the spleen of intact mice did not change under the influence of L. acidophilus ІМV В-7279, L. casei ІМV В-7280, B. animalis VKL or B. animalis VKB (individually). But, using L. acido­philus ІМV В-7279, L. casei ІМV В-7280, L. delbrueckii subsp. bulgaricus ІМV В-7281, B. animalis VKL and B. ani­malis VKB (individually) or their different compositions for colonization of the vagina in the case of intravaginal staphylococcosis associated with increasing of the number of NKC in spleen in different periods of observation. The number of NKC in the spleen of staphylococcus-infected mice completely normalized after treatment with some probiotic compositions. The probiotic bacteria (individually) only partially normalized the number of NKC in the spleen of staphylococcus-infected mice.

Conclusions. Thus, L. acidophilus ІМV В-7279, L. casei ІМV В-7280, L. delbrueckii subsp. bulgaricus ІМV В-7281 or B. animalis VKL (individually) or their various compositions are promising to create highly effective immunobiotics, that are able to increase the innate immunity in cases of infections.


M.B. Lodoen and L.L. Lanier, “Natural killer cells as an initial defense against pathogens”, Curr. Opin. Immunol., vol. 18, no. 4, pp. 391–398, 2006. doi: 10.1016/j.coi.2006.05.002

S. Schmidt et al., “Role of natural killer cells in antibacterial immunity”, Expert. Rev. Hematol., vol. 9, no. 12, pp. 1119–1127, 2016. doi: 10.1080/17474086.2016.1254546

M.A. Cooper et al., “NK cell and DC interactions”, Trends Immunol., vol. 25, no. 1, pp. 47–52, 2004. doi: 10.1016/

R. Reinhardt et al., “Invasive surgery impairs the regulatory function of human CD56 bright natural killer cells in response to Staphylococcus aureus. Suppression of Interferon-γ synthesis”, PLoS One, vol. 10, no. 6, e0130155, 2015. doi: 10.1371/journal.pone.0130155

W.-H. Sha et al., “The correlation between NK cell and liver function in patients with primary hepatocellular carcinoma”, Gut Liver, vol. 8, no. 3, pp. 298–305, 2014. doi: 10.5009/gnl.2014.8.3.298

H. Bruunsgaard et al., “Decreased natural killer cell activity is associated with atherosclerosis in elderly humans”, Exp. Gerontol., vol. 37, no. 1, pp. 127–136, 2001. doi: 10.1016/S0531-5565(01)00162-0

E.A. Ojo-Amaize et al., “Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome”, Clin. Infect. Dis., vol. 18, no. 1, pp. S157–S159, 1994.

H. Furue et al., “Decreased risk of colorectal cancer with the high natural killer cell activity NKG2D genotype in Japanese”, Carcinogenesis, vol. 29, no. 2, pp. 316–320, 2008. doi: 10.1093/carcin/bgm260

C.L. Small et al., “NKC play a critical protective role in host defense against acute extracellular Staphylococcus aureus bacterial infection in the lung”, J. Immunol., vol. 180, no. 8, pp. 5558–5568, 2008. doi: 10.4049/jimmunol.180.8.5558

M.E. Shirtliff and J.T. Mader, “Acute septic arthritis”, Clin. Microbiol. Rev., vol. 15, pp. 527–544, 2002. doi: 10.1128/CMR.15.4.527-544.2002

K. Hiramatsu et al., “The emergence and evolution of methicillin-resistant Staphylococcus aureus”, Trends Microbiol., vol. 9, pp. 486–493, 2001.

H. Zhao et al., “Exposure to particular matter increases susceptibility to respiratory Staphylococcus aureus infection in rats via reducing pulmonary natural killer cells”, Toxicology, vol. 5, no. 325, pp. 180–188, 2014. doi: 10.1016/j.tox.2014.09.006

N. Nilsson et al., “Protective role of NK1.1+ cells in experimental Staphylococcus aureus arthritis”, Clin. Exp. Immunol., vol. 117, no. 1, pp. 63–69, 1999. doi: 10.1046/j.1365-2249.1999.00922.x

S. Amdekar et al., “Probiotic therapy: immunomodulating approach toward urinary tract infection”, Curr. Microbiol., vol. 63, no. 5, pp. 484–490, 2011. doi: 10.1007/s00284-011-0006-2

R. Frei et al., “Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence, Curr. Opin. Gastroenterol., vol. 31, no. 2, pp. 153–158, 2015. doi: 10.1097/MOG.0000000000000151

L.N. Fink et al., “Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses”, Int. Immunol., vol. 19, no. 12, pp. 1319–1327, 2007. doi: 10.1093/intimm/dxm103

V. Rizzello et al., “Role of natural killer and dendritic cell crosstalk in immunomodulation by commensal bacteria probiotics”, J. Biomed. Biotechnol., vol. 2011, ID 473097, 2011. doi: 10.1155/2011/473097

T. Kawahara et al., “Consecutive oral administration of Bifidobacterium longum MM-2 improves the defense system against influenza virus infection by enhancing natural killer cell activity in a murine model”, Microbiol. Immunol., vol. 59, no. 1, pp. 1–12, 2015. doi: 10.1111/1348-0421.12210

J. Fan et al., “Effect of Bifidobacterium on the immunity in BALB/c mice”, Wei Sheng Wu Xue Bao, vol. 55, no. 4, pp. 484–491, 2015.

L. Lazarenko et al., “Antagonistic action of Lactobacilli and Bifidobacteria in relation to Staphylococcus aureus and their influence on the immune response in cases of intravaginal staphylococcosis in mice”, Probiotics Antimicrob Proteins., vol. 84, no. 3, pp. 78–89, 2012. doi: 10.1007/s12602-012-9093-z

M.Ya. Spivak et al., “Lactobacillus and Bifidobacterium influence the indices of immune response of the organism showed on experimental model”, Microbiol. Biotechnol., vol. 1, no. 5, pp. 39–46, 2009.

V.V. Мokrozub et al., “The role of beneficial bacteria wall elasticity in regulating innate immune response”, EPMA J., vol. 6, no. 1, p. 13, 2015. doi: 10.1186/s13167-015-0035-1

S. Koizumi et al., “Essential role of Toll-like receptors for dendritic cell and NK1.1(+) cell-dependent activation of type 1 immunity by Lactobacillus pentosus strain S-PT84”, Immunol. Lett., vol. 120, no. 1-2, pp. 14–19, 2008. doi: 10.1016/j.imlet.2008.06.003

Y. Fukui et al., “Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis”, Br. J. Nutr., vol. 110, no. 9, pp. 1617–1629, 2013. doi: 10.1017/S0007114513000767

X. Kou et al., “A tolerant lactic acid bacteria, Lactobacillus paracasei, and its immunoregulatory function”, Can. J. Microbiol., vol. 60, no. 11, pp. 729–736, 2014. doi: 10.1139/cjm-2014-0383

Y.D. Lee et al., “Differential cytokine regulatory effect of three Lactobacillus strains isolated from fermented foods”, J. Microbiol. Biotechnol., vol. 26, no. 9, pp. 1517–1526, 2016. doi: 10.4014/jmb.1601.01044

A. Takagi et al., “Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism”, Carcinogenesis, vol. 22, no. 4, pp. 599–605, 2001. doi: 10.1093/carcin/22.4.599

J.W. Lee et al., “Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum”, J. Vet. Sci., vol. 5, no. 1, pp. 41–48, 2004.

M.M. Soltan Dallal et al., “Lactobacillus casei ssp. casei induced Th1 cytokine profile and natural killer cells activity in invasive ductal carcinoma bearing mice”, Iran J. Allergy Asthma Immunol., vol. 11, no. 2, pp. 183–189, 2012. doi: 011.02/ijaai.183189