title: Variation in gamma interferon responses to different infecting strains of Mycobacterium tuberculosis in acid-fast bacillus smear-positive patients and household contacts in Antananarivo, Madagascar.
abstract: The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-gamma) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-gamma production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo, Madagascar, from 2004 to 2006 and examined the influence of the infecting M. tuberculosis strains on this response. The cohorts were sputum-positive index cases and their household contacts. Clinical strains isolated from the TB patients were typed by spoligotyping. Comparison of the IFN-gamma responses with the spoligotype of the infecting clinical strains showed that "modern" M. tuberculosis strains, like Beijing and Central Asian (CAS) strains, tended to induce lower IFN-gamma responses than "ancient" strains, like East African-Indian (EAI) strains, in index cases and their household contacts. These results suggest that new strains may have evolved to induce a host response different from that of ancient strains. These findings could have important implications in the development of therapeutic and diagnostic strategies.
authors.affiliation: Unité des Mycobactéries, Institut Pasteur de Madagascar, Ambatofotsikely BP 1274, Antananarivo 101, Madagascar.
authors.forename: Niaina
authors.initials: N
authors.lastname: Rakotosamimanana
authors.forename: Vaomalala
authors.initials: V
authors.lastname: Raharimanga
authors.forename: Soa Fy
authors.initials: SF
authors.lastname: Andriamandimby
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Soares
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Maherisoa
authors.initials: M
authors.lastname: Ratsitorahina
authors.forename: Herimanana
authors.initials: H
authors.lastname: Ramarokoto
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Jim
authors.initials: J
authors.lastname: Huggett
authors.forename: Graham
authors.initials: G
authors.lastname: Rook
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Voahangy
authors.initials: V
authors.lastname: Rasolofo-Razanamparany
mesh_terms: D000942:Antigens, Bacterial / Q000097:blood; D003625:Data Collection; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008270:Madagascar; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D013045:Species Specificity
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma
references.citation: PLoS One. 2009 Jun 16;4(6):e5930
references.pmid: 19529771
references.citation: J Clin Microbiol. 2007 Feb;45(2):409-14
references.pmid: 17166963
references.citation: J Clin Microbiol. 2007 Dec;45(12):3891-902
references.pmid: 17898156
references.citation: J Exp Med. 1997 Sep 15;186(6):859-65
references.pmid: 9294140
references.citation: Science. 1999 May 28;284(5419):1520-3
references.pmid: 10348738
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3684-9
references.pmid: 11891304
references.citation: Trends Mol Med. 2007 May;13(5):175-82
references.pmid: 17418641
references.citation: J Infect Dis. 2005 Dec 15;192(12):2059-65
references.pmid: 16288368
references.citation: Infect Genet Evol. 2005 Oct;5(4):340-8
references.pmid: 16168940
references.citation: Clin Vaccine Immunol. 2006 Feb;13(2):179-86
references.pmid: 16467323
references.citation: J Infect Dis. 2000 May;181(5):1850-4
references.pmid: 10823800
references.citation: Tuberculosis (Edinb). 2008 May;88(3):244-8
references.pmid: 18294915
references.citation: Curr Opin Pulm Med. 2009 May;15(3):188-200
references.pmid: 19387262
references.citation: J Clin Microbiol. 2005 May;43(5):2070-4
references.pmid: 15872224
references.citation: J Clin Microbiol. 2002 Nov;40(11):3964-9
references.pmid: 12409359
references.citation: Trans R Soc Trop Med Hyg. 2009 Jun;103(6):581-7
references.pmid: 19375139
references.citation: J Immunol. 2005 May 15;174(10):6332-9
references.pmid: 15879133
references.citation: PLoS Pathog. 2008 Mar 28;4(3):e1000034
references.pmid: 18369480
references.citation: J Immunol. 2004 Jun 1;172(11):6938-43
references.pmid: 15153513
references.citation: BMC Microbiol. 2006 Mar 06;6:23
references.pmid: 16519816
references.citation: Infect Immun. 1995 May;63(5):1710-7
references.pmid: 7729876
references.citation: Trends Microbiol. 2002 Jan;10(1):45-52
references.pmid: 11755085
references.citation: J Clin Microbiol. 2008 Apr;46(4):1363-8
references.pmid: 18287322
references.citation: J Clin Microbiol. 1997 Apr;35(4):907-14
references.pmid: 9157152
references.citation: BMC Infect Dis. 2006 Jul 05;6:105
references.pmid: 16820066
references.citation: Nature. 2004 Sep 2;431(7004):84-7
references.pmid: 15343336
references.citation: J Clin Microbiol. 2005 Nov;43(11):5779-81
references.pmid: 16272518
references.citation: Infect Immun. 2006 Dec;74(12):6865-76
references.pmid: 16982841
references.citation: Clin Microbiol Infect. 2007 Feb;13(2):120-128
references.pmid: 17328723
references.citation: Infect Immun. 2008 Jul;76(7):3027-36
references.pmid: 18443098
references.citation: J Infect Dis. 2005 Jul 1;192(1):98-106
references.pmid: 15942899
references.citation: Bull Soc Pathol Exot. 1997;90(5):349-52
references.pmid: 9507769
references.citation: J Infect Dis. 2005 Feb 1;191(3):453-60
references.pmid: 15633105
references.citation: J Biol Chem. 2009 Oct 2;284(40):27101-13
references.pmid: 19648652
references.citation: Immunology. 2004 Aug;112(4):669-73
references.pmid: 15270739
references.citation: Rev Tuberc Pneumol (Paris). 1963 Feb-Mar;27:217-72
references.pmid: 14018284
references.citation: Pediatr Infect Dis J. 2007 Jan;26(1):13-8
references.pmid: 17195699
references.citation: Clin Exp Immunol. 2004 Sep;137(3):460-8
references.pmid: 15320894
references.citation: Tuberculosis (Edinb). 2004;84(5):337-40
references.pmid: 15207809
references.citation: Infect Immun. 2004 Sep;72(9):5511-4
references.pmid: 15322056
references.citation: J Immunol. 2007 Apr 15;178(8):5217-26
references.pmid: 17404305
references.citation: Lancet. 2001 Jun 23;357(9273):2017-21
references.pmid: 11438135
references.citation: J Clin Microbiol. 2001 Apr;39(4):1530-5
references.pmid: 11283082
references.citation: J Clin Microbiol. 1991 Nov;29(11):2578-86
references.pmid: 1685494
references.citation: BMC Infect Dis. 2009 Feb 28;9:23
references.pmid: 19250549
references.citation: Clin Exp Immunol. 2003 Jul;133(1):30-7
references.pmid: 12823275
references.citation: J Clin Microbiol. 2007 May;45(5):1483-90
references.pmid: 17360841
references.citation: J Immunol. 2007 Jul 1;179(1):522-31
references.pmid: 17579073
references.citation: J Infect Dis. 2008 Oct 1;198(7):1037-43
references.pmid: 18702608
references.citation: Nat Rev Microbiol. 2005 Aug;3(8):656-62
references.pmid: 16012514
references.citation: Med Microbiol Immunol. 2009 Feb;198(1):33-7
references.pmid: 19034505
references.citation: Emerg Infect Dis. 2001 Sep-Oct;7(5):880-3
references.pmid: 11747703
references.citation: Ann Inst Pasteur (Paris). 1961 May;100:676-80
references.pmid: 13774765
references.citation: Am J Respir Crit Care Med. 2008 May 15;177(10):1164-70
references.pmid: 18276940
references.citation: J Infect Dis. 2004 Aug 15;190(4):756-66
references.pmid: 15272404
references.citation: Infect Immun. 2002 Oct;70(10):5446-53
references.pmid: 12228269
references.citation: Infect Immun. 1996 Jan;64(1):16-22
references.pmid: 8557334
references.citation: J Immunol Methods. 2005 Mar;298(1-2):129-41
references.pmid: 15847803
references.citation: J Clin Microbiol. 2002 Feb;40(2):704-6
references.pmid: 11826002
references.citation: Int J Tuberc Lung Dis. 2000 Dec;4(12):1181-3
references.pmid: 11144463
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2869-73
references.pmid: 16477032