Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy.
Neurocysticercosis (NCC) due to infection with Taenia solium is a major cause of epilepsy worldwide. Larval degeneration, which may follow antiparasitic treatment, results in clinical symptoms due to inflammatory cell influx. Mechanisms regulating this are not well understood, but chemokines have a key role. Stimulation of human monocytes by cyst Ags from NCC-infected pigs showed that scolex and membrane Ags drive CXCL8 and CCL2 secretion. Antiparasitic treatment of pigs increased CXCL8 in response to brain, but not muscle, cyst Ags. Cyst-fluid Ags did not elicit monocyte chemokine secretion, inhibited LPS-induced CXCL8 by up to 89%, but did not alter CCL2 secretion. This effect was inhibited by anti-IL-10 Abs. Plasma CXCL8, TNF-α, IL-10, eotaxin, IL-1, IL-1ra, soluble IL-1R-II, and soluble TNFR-I and -II levels were evaluated in 167 NCC patients. Patients had lower plasma CXCL8 and TNF-α concentrations than control subjects. In summary, larval Ags from brain and muscle cysts differentially regulate chemokine secretion. Cyst-fluid inhibits CXCL8, and this is blocked by anti-IL-10 Abs. CXCL8 concentrations are decreased in patient plasma. Following anti-parasitic therapy, scolex and membrane Ags are exposed, and cyst fluid is decreased, leading to inflammatory cell influx. Taken together, the cellular, porcine, and human data may explain, in part, why NCC is usually asymptomatic but may cause proinflammatory symptoms, particularly following treatment.
Uddin
Jasim
J
Department of Infectious Diseases and Immunity, Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College London, London, United Kingdom.
Gonzalez
Armando E
AE
Gilman
Robert H
RH
Thomas
Lynette H
LH
Rodriguez
Silvia
S
Evans
Carlton A W
CA
Remick
Daniel G
DG
Garcia
Hector H
HH
Friedland
Jon S
JS
D000818:Animals; D000947:Antigens, Helminth; D000977:Antiparasitic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D003560:Cysts / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D020019:Neurocysticercosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D013552:Swine
D000947:Antigens, Helminth; D000977:Antiparasitic Agents; D018925:Chemokines; D016209:Interleukin-8
Parasitol Res. 2003 Mar;89(5):407-13
12632156
Immunol Rev. 2008 Dec;226:205-18
19161426
J Immunol. 1999 Jan 15;162(2):995-1002
9916725
Parasitol Res. 1996;82(7):590-7
8875565
J Parasitol. 2006 Aug;92(4):738-41
16995390
J Parasitol. 2001 Jun;87(3):587-90
11426722
Biochim Biophys Acta. 1972 Jan 28;261(1):284-9
4551964
Am J Trop Med Hyg. 2001 Oct;65(4):366-70
11693886
Am J Trop Med Hyg. 1996 Apr;54(4):391-4
8615453
Am J Med. 1989 Aug;87(2):139-43
2667356
Clin Immunol Immunopathol. 1995 Jul;76(1 Pt 1):32-6
7606866
J Neuroimmunol. 1998 Aug 14;89(1-2):64-72
9726827
J Immunol. 2005 Sep 1;175(5):3273-81
16116219
J Infect Dis. 1989 Jan;159(1):50-9
2909643
Int J Parasitol. 2008 Feb;38(2):239-48
17765901
Curr Opin Infect Dis. 2003 Oct;16(5):411-9
14501993
J Neuroimmunol. 2009 Jan 3;206(1-2):118-20
18947884
Immunol Invest. 1990 Feb;19(1):69-79
2110931
Anal Biochem. 1976 May 7;72:248-54
942051
Infect Immun. 1998 Sep;66(9):4522-5
9712812
Microbes Infect. 2006 Jun;8(7):1732-40
16815071
Parasite Immunol. 2001 Jan;23(1):1-9
11136472
Parasitol Int. 2006;55 Suppl:S111-5
16330240
J Exp Med. 2001 Nov 19;194(10):1497-506
11714756
Parasite. 2002 Dec;9(4):351-6
12514950
Clin Exp Immunol. 2001 Nov;126(2):304-10
11703375
J Immunol. 2002 Apr 1;168(7):3135-9
11907063
J Neuroimmunol. 2000 Apr 3;104(1):92-7
10683519
Ann Trop Med Parasitol. 1997 Sep;91(6):627-32
9425365
Parasitology. 1996 Jun;112 ( Pt 6):561-70
8684830
Immunol Invest. 1991 Feb;20(1):89-97
2055605
J Neurovirol. 1999 Feb;5(1):3-12
10190685
J Immunol. 2002 May 1;168(9):4620-7
11971010
J Immunol. 1993 Nov 15;151(10):5461-71
8228238
Parasitol Res. 1998;84(2):117-22
9493210
Neurology. 2006 Oct 10;67(7):1120-7
17030744
Parasitol Res. 2005 Mar;95(4):256-65
15678353
Lancet. 1998 Mar 28;351(9107):950-3
9734942
J Immunol. 1996 Jun 15;156(12):4715-21
8648117
Infect Immun. 2003 May;71(5):2634-42
12704138
Scand J Immunol. 1990 Feb;31(2):205-11
2106723
Infect Immun. 1997 Jul;65(7):2925-31
9199468
Lancet. 1986 Dec 13;2(8520):1364-5
2878227
Braz J Med Biol Res. 2000 Sep;33(9):1059-63
10973138
N Engl J Med. 1992 Sep 3;327(10):692-5
1495521
J Parasitol. 1992 Apr;78(2):281-7
1556644
Microbes Infect. 2006 Apr;8(4):1082-9
16520076
Emerg Infect Dis. 2002 Jun;8(6):608-13
12023918
Clin Microbiol Rev. 2002 Oct;15(4):747-56
12364377
Infect Immun. 2001 Apr;69(4):2470-6
11254609
PLoS Negl Trop Dis. 2008 Sep 24;2(9):e300
18820747
Lancet Neurol. 2005 Oct;4(10):653-61
16168934
Nature. 2000 Mar 23;404(6776):407-11
10746730
J Infect Dis. 2000 Jan;181(1):176-80
10608764