title: Mouse eosinophils possess potent antibacterial properties in vivo.
abstract: Eosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils, suggesting that these leukocytes may participate in the recognition and killing of viruses and bacteria. However, the significance of this role in the innate immune response to bacterial infection is largely unknown. Here we report a novel role for eosinophils as antibacterial defenders in the host response. Isolated mouse eosinophils possessed antipseudomonal properties in vitro. In vivo, interleukin-5 transgenic mice, which have profound eosinophilia, demonstrated improved clearance of Pseudomonas aeruginosa introduced into the peritoneal cavity. The findings of improved bacterial clearance following adoptive transfer of eosinophils, and impaired bacterial clearance in mice with a congenital eosinophil deficiency, established that this effect was eosinophil specific. The data presented also demonstrate that eosinophils mediate this antibacterial effect in part through the release of cationic secondary granule proteins. Specifically, isolated eosinophil granules had antibacterial properties in vitro, and administration of eosinophil granule extracts significantly improved bacterial clearance in vivo. These data suggest a potent yet underappreciated antibacterial role for eosinophils in vivo, specifically for eosinophil granules. Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.
authors.affiliation: Oregon Health and Science University, Division of Pulmonary and Critical Care Medicine, 3181 SW Sam Jackson Park Rd., Mail Code UHN67, Portland, OR 97239, USA.
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Linch
authors.forename: Ann M
authors.initials: AM
authors.lastname: Kelly
authors.forename: Erin T
authors.initials: ET
authors.lastname: Danielson
authors.forename: Ralph
authors.initials: R
authors.lastname: Pero
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gold
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology*; D047150:Eosinophil Cationic Protein / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011552:Pseudomonas Infections / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D015848:Interleukin-5; D047150:Eosinophil Cationic Protein
references.citation: Clin Immunol. 2005 Jan;114(1):61-9
references.pmid: 15596410
references.citation: Intensive Care Med. 2000 Apr;26(4):364-75
references.pmid: 10872127
references.citation: Infect Immun. 1984 May;44(2):534-6
references.pmid: 6325350
references.citation: Rev Infect Dis. 1980 May-Jun;2(3):505-17
references.pmid: 6251530
references.citation: Arch Surg. 1985 Jan;120(1):93-8
references.pmid: 2981524
references.citation: Am J Respir Crit Care Med. 2002 Jul 15;166(2):138-43
references.pmid: 12119223
references.citation: Infect Immun. 2001 Jun;69(6):3591-6
references.pmid: 11349018
references.citation: Nature. 2002 Dec 19-26;420(6917):885-91
references.pmid: 12490963
references.citation: Crit Care Med. 1989 Dec;17(12):1241-6
references.pmid: 2556243
references.citation: J Immunol. 1989 Jun 15;142(12):4428-34
references.pmid: 2656865
references.citation: Lancet. 2000 Sep 16;356(9234):961-7
references.pmid: 11041396
references.citation: Chest. 2005 Jun;127(6):2139-50
references.pmid: 15947332
references.citation: Clin Infect Dis. 2004 Feb 1;38(3):460-1
references.pmid: 14727227
references.citation: Shock. 1995 Aug;4(2):89-95
references.pmid: 7496903
references.citation: J Immunol. 2003 Oct 15;171(8):3977-82
references.pmid: 14530316
references.citation: Am J Respir Cell Mol Biol. 2007 Jul;37(1):85-96
references.pmid: 17332440
references.citation: Clin Exp Immunol. 2009 Jun;156(3):552-61
references.pmid: 19438610
references.citation: J Clin Invest. 1975 Oct;56(4):870-9
references.pmid: 1099120
references.citation: Crit Care Med. 2001 Jul;29(7):1303-10
references.pmid: 11445675
references.citation: Nat Med. 2008 Sep;14(9):949-53
references.pmid: 18690244
references.citation: N Engl J Med. 2003 Jan 9;348(2):138-50
references.pmid: 12519925
references.citation: Crit Care. 2007;11(2):R49
references.pmid: 17448250
references.citation: Curr Opin Infect Dis. 1998 Jun;11(3):279-83
references.pmid: 17033392
references.citation: Shock. 2005 Dec;24 Suppl 1:52-7
references.pmid: 16374373
references.citation: J Exp Med. 1991 Sep 1;174(3):649-55
references.pmid: 1875165
references.citation: Crit Care Med. 1997 Jul;25(7):1115-24
references.pmid: 9233735
references.citation: J Clin Invest. 1980 Jun;65(6):1265-71
references.pmid: 7410543
references.citation: Blood. 2007 Jun 1;109(11):4716-23
references.pmid: 17311988
references.citation: Clin Diagn Lab Immunol. 1995 Sep;2(5):549-53
references.pmid: 8548533
references.citation: Infect Immun. 1992 Nov;60(11):4754-61
references.pmid: 1398985
references.citation: Lancet. 1998 Mar 28;351(9107):929-33
references.pmid: 9734938
references.citation: Infect Immun. 2003 Jun;71(6):3521-8
references.pmid: 12761137
references.citation: Am J Med. 1952 Jul;13(1):58-72
references.pmid: 12976408
references.citation: Science. 2004 Sep 17;305(5691):1773-6
references.pmid: 15375267
references.citation: J Immunol. 1997 Feb 1;158(3):1332-44
references.pmid: 9013977
references.citation: Ann Med. 2002;34(7-8):614-23
references.pmid: 12553502
references.citation: J Exp Med. 2008 Mar 17;205(3):699-710
references.pmid: 18316417
references.citation: Chest. 2000 Jul;118(1):146-55
references.pmid: 10893372
references.citation: Eur J Clin Invest. 1995 Sep;25(9):687-92
references.pmid: 7498244
references.citation: N Engl J Med. 2003 Apr 17;348(16):1546-54
references.pmid: 12700374
references.citation: Arch Surg. 2006 Feb;141(2):150-3; discussion 154
references.pmid: 16490891
references.citation: Infect Immun. 2003 Feb;71(2):605-13
references.pmid: 12540536
references.citation: Am J Respir Crit Care Med. 1996 Feb;153(2):684-93
references.pmid: 8564118
references.citation: Crit Care Med. 1998 May;26(5):895-904
references.pmid: 9590320
references.citation: J Leukoc Biol. 2001 Nov;70(5):691-8
references.pmid: 11698487
references.citation: Microbes Infect. 2005 Apr;7(4):720-8
references.pmid: 15857806
references.citation: Blood. 1998 Jun 15;91(12):4770-5
references.pmid: 9616176
references.citation: J Immunol. 2006 Aug 1;177(3):1833-7
references.pmid: 16849494
references.citation: Crit Care Med. 1996 Sep;24(9):1431-40
references.pmid: 8797612
references.citation: J Immunol. 1998 May 15;160(10):5082-7
references.pmid: 9590259
references.citation: J Clin Invest. 1992 Sep;90(3):1122-30
references.pmid: 1522221
references.citation: Crit Care. 2008;12(2):R59
references.pmid: 18435836
references.citation: Blood. 2007 Sep 1;110(5):1578-86
references.pmid: 17495130
references.citation: Nat Med. 1997 Jun;3(6):678-81
references.pmid: 9176497