Mouse eosinophils possess potent antibacterial properties in vivo.
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.
Linch
Stefanie N
SN
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.
Kelly
Ann M
AM
Danielson
Erin T
ET
Pero
Ralph
R
Lee
James J
JJ
Gold
Jeffrey A
JA
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*
D000900:Anti-Bacterial Agents; D015848:Interleukin-5; D047150:Eosinophil Cationic Protein
Clin Immunol. 2005 Jan;114(1):61-9
15596410
Intensive Care Med. 2000 Apr;26(4):364-75
10872127
Infect Immun. 1984 May;44(2):534-6
6325350
Rev Infect Dis. 1980 May-Jun;2(3):505-17
6251530
Arch Surg. 1985 Jan;120(1):93-8
2981524
Am J Respir Crit Care Med. 2002 Jul 15;166(2):138-43
12119223
Infect Immun. 2001 Jun;69(6):3591-6
11349018
Nature. 2002 Dec 19-26;420(6917):885-91
12490963
Crit Care Med. 1989 Dec;17(12):1241-6
2556243
J Immunol. 1989 Jun 15;142(12):4428-34
2656865
Lancet. 2000 Sep 16;356(9234):961-7
11041396
Chest. 2005 Jun;127(6):2139-50
15947332
Clin Infect Dis. 2004 Feb 1;38(3):460-1
14727227
Shock. 1995 Aug;4(2):89-95
7496903
J Immunol. 2003 Oct 15;171(8):3977-82
14530316
Am J Respir Cell Mol Biol. 2007 Jul;37(1):85-96
17332440
Clin Exp Immunol. 2009 Jun;156(3):552-61
19438610
J Clin Invest. 1975 Oct;56(4):870-9
1099120
Crit Care Med. 2001 Jul;29(7):1303-10
11445675
Nat Med. 2008 Sep;14(9):949-53
18690244
N Engl J Med. 2003 Jan 9;348(2):138-50
12519925
Crit Care. 2007;11(2):R49
17448250
Curr Opin Infect Dis. 1998 Jun;11(3):279-83
17033392
Shock. 2005 Dec;24 Suppl 1:52-7
16374373
J Exp Med. 1991 Sep 1;174(3):649-55
1875165
Crit Care Med. 1997 Jul;25(7):1115-24
9233735
J Clin Invest. 1980 Jun;65(6):1265-71
7410543
Blood. 2007 Jun 1;109(11):4716-23
17311988
Clin Diagn Lab Immunol. 1995 Sep;2(5):549-53
8548533
Infect Immun. 1992 Nov;60(11):4754-61
1398985
Lancet. 1998 Mar 28;351(9107):929-33
9734938
Infect Immun. 2003 Jun;71(6):3521-8
12761137
Am J Med. 1952 Jul;13(1):58-72
12976408
Science. 2004 Sep 17;305(5691):1773-6
15375267
J Immunol. 1997 Feb 1;158(3):1332-44
9013977
Ann Med. 2002;34(7-8):614-23
12553502
J Exp Med. 2008 Mar 17;205(3):699-710
18316417
Chest. 2000 Jul;118(1):146-55
10893372
Eur J Clin Invest. 1995 Sep;25(9):687-92
7498244
N Engl J Med. 2003 Apr 17;348(16):1546-54
12700374
Arch Surg. 2006 Feb;141(2):150-3; discussion 154
16490891
Infect Immun. 2003 Feb;71(2):605-13
12540536
Am J Respir Crit Care Med. 1996 Feb;153(2):684-93
8564118
Crit Care Med. 1998 May;26(5):895-904
9590320
J Leukoc Biol. 2001 Nov;70(5):691-8
11698487
Microbes Infect. 2005 Apr;7(4):720-8
15857806
Blood. 1998 Jun 15;91(12):4770-5
9616176
J Immunol. 2006 Aug 1;177(3):1833-7
16849494
Crit Care Med. 1996 Sep;24(9):1431-40
8797612
J Immunol. 1998 May 15;160(10):5082-7
9590259
J Clin Invest. 1992 Sep;90(3):1122-30
1522221
Crit Care. 2008;12(2):R59
18435836
Blood. 2007 Sep 1;110(5):1578-86
17495130
Nat Med. 1997 Jun;3(6):678-81
9176497