Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through gamma delta T-cell IL-17 production in a murine model of sepsis.
The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-γ) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by γδ T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.
Kasten
Kevin R
KR
Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA.
Prakash
Priya S
PS
Unsinger
Jacqueline
J
Goetzman
Holly S
HS
England
Lisa G
LG
Cave
Cindy M
CM
Seitz
Aaron P
AP
Mazuski
Cristina N
CN
Zhou
Tony T
TT
Morre
Michel
M
Hotchkiss
Richard S
RS
Hildeman
David A
DA
Caldwell
Charles C
CC
D000818:Animals; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
D016207:Cytokines; D020381:Interleukin-17; D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta
Intensive Care Med. 2004 Mar;30(3):408-15
14722631
PLoS One. 2007 Sep 05;2(9):e853
17786224
Shock. 2005 Jul;24(1):40-7
15988319
Blood. 2001 Feb 1;97(3):601-7
11157474
BMC Immunol. 2010 Jan 25;11:4
20100328
J Leukoc Biol. 2005 Aug;78(2):325-37
15817707
Nature. 1995 Jan 19;373(6511):255-7
7816142
Immunity. 2009 Aug 21;31(2):321-30
19682928
Shock. 2008 May;29(5):591-7
17885647
Shock. 2007 Nov;28(5):576-81
18084824
Nat Rev Immunol. 2003 Mar;3(3):233-42
12658271
J Immunol. 2010 Apr 1;184(7):3768-79
20200277
Shock. 2007 Sep;28(3):334-8
17545945
Infect Immun. 2009 Jan;77(1):485-91
19001080
J Immunol. 1994 May 15;152(10):5014-21
8176219
Crit Care Med. 2001 Jul;29(7):1303-10
11445675
Blood. 2008 Jan 1;111(1):42-9
17928531
J Exp Med. 2008 Jul 7;205(7):1701-14
18573906
J Immunol. 2001 Jun 1;166(11):6952-63
11359857
Cytokine Growth Factor Rev. 1998 Jun;9(2):167-73
9754710
Shock. 2007 May;27(5):507-19
17438456
Inflamm Res. 2010 Oct;59(10):809-16
20372968
Shock. 2003 Aug;20(2):123-9
12865655
Immunity. 2009 Aug 21;31(2):331-41
19682929
Lancet. 2004 May 22;363(9422):1721-3
15158636
Shock. 2010 Oct;34(4):377-83
20610943
Annu Rev Immunol. 2007;25:821-52
17201677
Nat Rev Immunol. 2009 Aug;9(8):556-67
19575028
J Immunol. 1999 Aug 1;163(3):1537-44
10415057
Crit Care Med. 1999 Jul;27(7):1230-51
10446814
Shock. 1999 Aug;12(2):118-26
10446892
J Virol. 2009 Sep;83(17):8604-15
19515766
J Immunol. 2009 Jun 15;182(12):7846-54
19494309
Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1338-43
16793935
J Immunother. 2006 May-Jun;29(3):313-9
16699374
J Immunol. 2005 Apr 15;174(8):5110-8
15814742
J Immunol. 2001 Dec 1;167(11):6140-9
11714773
Shock. 2002 Dec;18(6):487-94
12462554
Eur J Immunol. 1997 Jul;27(7):1704-12
9247581
Shock. 2002 Jun;17(6):463-7
12069181
Annu Rev Immunol. 2007;25:193-219
17129180
Immunology. 2003 Mar;108(3):365-74
12603603
Biochem Biophys Res Commun. 2007 Sep 21;361(2):533-6
17662241
Curr Opin Immunol. 2008 Jun;20(3):353-7
18439808
Blood. 1998 Dec 15;92(12):4742-9
9845540
J Immunol. 1999 Apr 1;162(7):4148-56
10201940
Methods Enzymol. 1986;132:198-204
3102897
Blood. 1997 Aug 1;90(3):909-28
9242519
FASEB J. 2008 Jul;22(7):2198-205
18299333
J Virol. 2008 Oct;82(19):9564-76
18667515
J Immunol. 2000 Jun 15;164(12):6322-31
10843686
J Exp Med. 2001 Aug 20;194(4):519-27
11514607
J Leukoc Biol. 2004 Mar;75(3):443-52
14673016
Adv Immunol. 2005;87:27-59
16102571
Blood. 2001 Dec 1;98(12):3309-14
11719368
Shock. 2010 Oct;34(4):327-36
20386500
Nat Rev Immunol. 2006 Nov;6(11):813-22
17039247
J Exp Med. 1996 Jun 1;183(6):2593-603
8676080
Shock. 2010 Oct;34(4):358-63
20220566
Mol Med. 2008 Jan-Feb;14(1-2):64-78
18026569
J Immunol. 2002 Apr 1;168(7):3195-204
11907072
J Leukoc Biol. 2008 Mar;83(3):581-8
18063696