Probiotic Lactobacillus casei activates innate immunity via NF-κB and p38 MAP kinase signaling pathways

Yun Gi Kim, Toshihisa Ohta, Takuya Takahashi, Akira Kushiro, Koji Nomoto, Teruo Yokokura, Nobuhiko Okada, Hirofumi Danbara

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


Probiotic bacteria are microorganisms that benefit the host through improvement of the balance of intestinal microflora and possibly by augmentation of host defense systems. We examined the mechanisms for the up-regulation of innate immune responses by a probiotic Lactobacillus casei ATCC27139, in vivo. Using mouse models of systemic Listeria monocytogenes infection and MethA fibrosarcoma tumorigenesis in combination with BALB/c and SCID mice, we found that parenteral administration of L. casei ATCC27139 confers a protective effect against L. monocytogenes infection and anti-tumor activity against MethA fibrosarcoma by activation of innate immunity, while L. casei ATCC27139-J1R strains, which are J1 phage-resistant strains that have been selected from MNNG-treated clones, lacked these activities. Substantial differences between ATCC27139 and ATCC27139-J1R strains were observed in the capacity to induce innate cytokines such as TNF-α, IL-12, IL-18, and IFN-γ, and pathogen-associated molecular pattern receptors, TLR2 and Nod2, by spleen cells. In addition, although phosphorylation of NF-κB p65 in spleen was equally enhanced in the ATCC27139- and the ATCC27139-J1R-treated groups, phosphorylation of both p38 MAPK and MAPKAPK-2 was significantly induced only by ATCC27139. Furthermore, inhibitors of NF-κB (sulfasalazine) and p38 MAPK (SB203580) significantly reduced cytokine production by the spleen cells of the mice treated with L. casei ATCC27139, suggesting that both NF-κB and p38 MAPK signaling pathways play important roles in the augmentation of innate immunity by the probiotic L. casei.

Original languageEnglish
Pages (from-to)994-1005
Number of pages12
JournalMicrobes and Infection
Issue number4
Publication statusPublished - 2006 Apr
Externally publishedYes


  • Innate immunity
  • Lactobacillus
  • Mouse model
  • Pathogen-associated molecular pattern receptors
  • Probiotics
  • Signal transduction

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases


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