title: CCR9+ macrophages are required for eradication of peritoneal bacterial infections and prevention of polymicrobial sepsis.
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.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors: Takahiro
authors: T
authors: Mizukami
authors: Takanori
authors: T
authors: Kanai
authors: Yohei
authors: Y
authors: Mikami
authors: Atsushi
authors: A
authors: Hayashi
authors: Tomomitsu
authors: T
authors: Doi
authors: Tango
authors: T
authors: Handa
authors: Atsuhiro
authors: A
authors: Matsumoto
authors: Li
authors: L
authors: Jun
authors: Katsuyoshi
authors: K
authors: Matsuoka
authors: Toshiro
authors: T
authors: Sato
authors: Tadakazu
authors: T
authors: Hisamatsu
authors: Toshifumi
authors: T
authors: Hibi
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D010529:Peritoneal Cavity / Q000382:microbiology / Q000473:pathology; D010532:Peritoneal Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D054388:Receptors, CCR / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: C119309:CC chemokine receptor 9; D016207:Cytokines; D018836:Inflammation Mediators; D054388:Receptors, CCR