CCR9+ macrophages are required for eradication of peritoneal bacterial infections and prevention of polymicrobial sepsis

Takahiro Mizukami, Takanori Kanai, Yohei Mikami, Atsushi Hayashi, Tomomitsu Doi, Tango Handa, Atsuhiro Matsumoto, Li Jun, Katsuyoshi Matsuoka, Toshiro Sato, Tadakazu Hisamatsu, Toshifumi Hibi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Sepsis is a systemic inflammatory response to infection associated with multiple organ dysfunction syndrome and a high mortality rate. In septic shock induced by severe peritonitis, early response of peritoneal macrophages against infected microbes is vital in preventing the spread of infection. We found that the mucosal homing receptor CCR9, is induced in peritoneal macrophages in response to inflammatory stimulation. We used a cecal ligation and puncture (CLP) model of sepsis to determine the role of CCR9 with respect to peritoneal macrophages, and controlling peritoneal infection and systemic inflammation. CCR9-/- mice showed aggravated septic shock with higher mortality rates compared with wild-type (WT) mice. Six hours after CLP, CCR9-/- mice demonstrated a greater inflammatory response. This was associated with higher production of inflammatory cytokines, such as IL-6, TNF and IP-10 in peritoneal lavage compared with WT mice. Although the numbers of peritoneal bacteria were elevated in CCR9-/- mice subjected to CLP compared with WT mice, this was normalized in CCR9-/- mice subjected to CLP through the adoptive transfer of WT peritoneal macrophages. We conclude that CCR9 is required for recruitment of peritoneal macrophages in the steady state to control systemic sepsis during early phases of peritoneal infection.

Original languageEnglish
Pages (from-to)75-79
Number of pages5
JournalImmunology Letters
Volume147
Issue number1-2
DOIs
Publication statusPublished - 2012 Sep 1

Keywords

  • CCR9
  • Macrophages
  • Peritonitis
  • Sepsis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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