Innate immune response in Th1- and Th2-dominant mouse strains

Hiroyuki Watanabe, Kousuke Numata, Takaaki Ito, Katsumasa Takagi, Akihiro Matsukawa

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

C57BL/6 and BALB/c mice are prototypical Th1- and Th2-type mouse strains, respectively. In the present study, we attempted to characterize the innate immune response of macrophages from these mouse strains. Macrophages from C57BL/6 mice produced higher levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-12 than those from BALB/c mice after stimulation with macrophage-activating lipopeptide-2 (MALP-2, a synthetic TLR-2 ligand) or lipopolysaccharide (LPS, a TLR-4 ligand). The augmented IL-12 production by C57BL/6 macrophages increased interferon-γ and, in contrast, decreased IL-13 production by CD4+ T cells. On stimulation with MALP-2 or LPS, C57BL/6 macrophages produced lysosomal enzyme and nitric oxide, effector molecules for bacterial killing, whereas BALB/c macrophages did not. Bactericidal activity of BALB/c macrophages was impaired relative to C57BLV6 macrophages when cells were infected with live bacteria in vitro. In a murine model of septic peritonitis induced by cecal ligation and puncture (CLP), BALB/c mice failed to facilitate bacterial clearance relative to C57BLV6 mice despite an augmented peritoneal leukocyte infiltration that was associated with increased peritoneal levels of cytokines/chemokines. BALB/c mice exhibited increased plasma and hepatic levels of cytokines/chemokines, resulting in an exaggerated systemic inflammation as determined by acute-phase proteins. Finally, BALB/c mice were vulnerable to CLP-induced lethality relative to C57BLV6 mice. Altogether, innate immune response of macrophages is different between these mouse strains, which may affect the development of Th1 and Th2 adaptive immunity in these strains. Reduced systemic inflammatory response in C57BL/6 mice that may result from an eminent local response appears to be beneficial during sepsis.

Original languageEnglish
Pages (from-to)460-466
Number of pages7
JournalShock
Volume22
Issue number5
DOIs
Publication statusPublished - Nov 2004
Externally publishedYes

Fingerprint

Innate Immunity
Macrophages
Interleukin-12
Inbred C57BL Mouse
Punctures
Chemokines
Ligation
Cytokines
Ligands
Lipopeptides
Interleukin-13
Acute-Phase Proteins
Adaptive Immunity
Peritonitis
Interferons
Lipopolysaccharides
Sepsis
Nitric Oxide
Leukocytes
Tumor Necrosis Factor-alpha

Keywords

  • Bactericidal activity
  • Cecal ligation and puncture
  • Chemokines
  • Cytokines
  • Macrophages
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Innate immune response in Th1- and Th2-dominant mouse strains. / Watanabe, Hiroyuki; Numata, Kousuke; Ito, Takaaki; Takagi, Katsumasa; Matsukawa, Akihiro.

In: Shock, Vol. 22, No. 5, 11.2004, p. 460-466.

Research output: Contribution to journalArticle

Watanabe, Hiroyuki ; Numata, Kousuke ; Ito, Takaaki ; Takagi, Katsumasa ; Matsukawa, Akihiro. / Innate immune response in Th1- and Th2-dominant mouse strains. In: Shock. 2004 ; Vol. 22, No. 5. pp. 460-466.
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