title: Immunohistological characterization of spinal TB granulomas from HIV-negative and -positive patients.
abstract: Tuberculosis (TB) is mainly a disease of the lungs, but Mycobacterium tuberculosis (Mtb) can establish infection in virtually any organ in the body. Rising rates of extrapulmonary (EP) TB have been largely associated with the HIV epidemic, as patients co-infected with HIV show a four-fold higher risk of EPTB. Spinal TB (Pott's Disease), one of the most debilitating extrapulmonary forms of disease, is difficult to diagnose and can cause deformity and/or neurological deficits. This study examined the histopathology and distribution of immune cells within spinal TB lesions and the impact of HIV on pathogenesis. The overall structure of the spinal granulomas resembled that seen in lung lesions from patients with pulmonary TB. Evidence of efficient macrophage activation and differentiation were detectable within organized structures in the spinal tissue, irrespective of HIV status. Interestingly, the granulomatous architecture and macroscopic features were similar in all samples examined, despite a reversal in the ratio of infiltrating CD4 to CD8 T cells in the lesions from HIV-infected patients. This study provides a foundation to understand the mechanism of tissue destruction and disease progression in Spinal TB, enabling the future development of novel therapeutic strategies and diagnostic approaches for this devastating disease.
authors.affiliation: Virology Laboratory, Africa Centre for Health and Population Studies, Doris Duke Medical Research Institute (DDMRI) at University of KwaZulu-Natal (UKZN), Durban 4013, South Africa. sdanaviah@africacentre.ac.za
authors.forename: S
authors.initials: S
authors.lastname: Danaviah
authors.forename: J A
authors.initials: JA
authors.lastname: Sacks
authors.forename: K P S
authors.initials: KP
authors.lastname: Kumar
authors.forename: L M
authors.initials: LM
authors.lastname: Taylor
authors.forename: D A
authors.initials: DA
authors.lastname: Fallows
authors.forename: T
authors.initials: T
authors.lastname: Naicker
authors.forename: T
authors.initials: T
authors.lastname: Ndung'u
authors.forename: S
authors.initials: S
authors.lastname: Govender
authors.forename: G
authors.initials: G
authors.lastname: Kaplan
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D000038:Abscess / Q000276:immunology / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D016723:Bone Remodeling / Q000502:physiology; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014399:Tuberculosis, Spinal / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019562:Viral Load; D055815:Young Adult
references.citation: PLoS One. 2011;6(7):e22637
references.pmid: 21829471
references.citation: J Exp Med. 2010 Dec 20;207(13):2869-81
references.pmid: 21115690
references.citation: Am J Respir Cell Mol Biol. 2011 Dec;45(6):1116-24
references.pmid: 21852682
references.citation: Immunol Rev. 2011 Mar;240(1):252-68
references.pmid: 21349098
references.citation: Am J Respir Crit Care Med. 2010 Apr 1;181(7):734-42
references.pmid: 20019339
references.citation: Infect Immun. 2003 Dec;71(12):7099-108
references.pmid: 14638800
references.citation: J Indian Med Assoc. 2011 Mar;109(3):161-5
references.pmid: 22010584
references.citation: Clin Dev Immunol. 2012;2012:139127
references.pmid: 22811737
references.citation: Int Orthop. 2012 Feb;36(2):245-54
references.pmid: 22215363
references.citation: Infect Immun. 2008 Jan;76(1):78-88
references.pmid: 17938213
references.citation: J Immunol. 2007 Mar 1;178(5):3161-9
references.pmid: 17312164
references.citation: EMBO Mol Med. 2010 Jul;2(7):258-74
references.pmid: 20597103
references.citation: PLoS One. 2009 Jul 01;4(7):e6116
references.pmid: 19568431
references.citation: J Exp Med. 2000 Aug 7;192(3):347-58
references.pmid: 10934223
references.citation: Immunol Cell Biol. 2007 Feb-Mar;85(2):103-11
references.pmid: 17213830
references.citation: Int Orthop. 2003;27(4):244-8
references.pmid: 12715238
references.citation: J Acquir Immune Defic Syndr. 2000 Aug 15;24(5):408-17
references.pmid: 11035611
references.citation: Am J Respir Cell Mol Biol. 2003 Jul;29(1):28-38
references.pmid: 12600829
references.citation: Eur Rev Med Pharmacol Sci. 2012 Apr;16 Suppl 2:73-8
references.pmid: 22655485
references.citation: J Virol. 2002 Feb;76(4):1697-706
references.pmid: 11799165
references.citation: Curr Opin HIV AIDS. 2012 May;7(3):268-75
references.pmid: 22495739
references.citation: Thorax. 2009 Dec;64(12):1090-5
references.pmid: 19850965
references.citation: Clin Orthop Relat Res. 2007 Jul;460:50-5
references.pmid: 17471104
references.citation: PLoS Pathog. 2011 May;7(5):e1002052
references.pmid: 21625591
references.citation: J Bone Joint Surg Br. 2001 Aug;83(6):864-7
references.pmid: 11521930
references.citation: Clin Dev Immunol. 2011;2011:
references.pmid: 20871843
references.citation: Nat Rev Immunol. 2012 Apr 20;12(5):352-66
references.pmid: 22517424
references.citation: Curr Opin Microbiol. 2012 Feb;15(1):63-70
references.pmid: 22074861
references.citation: Int Orthop. 2012 Feb;36(2):221-31
references.pmid: 22116392
references.citation: Indian J Orthop. 2012 Mar;46(2):186-90
references.pmid: 22448057
references.citation: Radiology. 1994 Oct;193(1):115-9
references.pmid: 7916467
references.citation: Infect Immun. 2011 Apr;79(4):1407-17
references.pmid: 21245275
references.citation: Immunology. 2006 Apr;117(4):454-62
references.pmid: 16556259
references.citation: J Immunol. 2006 Oct 15;177(8):5647-51
references.pmid: 17015753
references.citation: J Pathol. 2007 Jan;211(1):76-85
references.pmid: 17115379
references.citation: Eur J Immunol. 2005 Aug;35(8):2367-75
references.pmid: 16025563
references.citation: Eur Spine J. 2013 Jun;22 Suppl 4:624-33
references.pmid: 22565802
references.citation: Science. 2010 Jan 22;327(5964):466-9
references.pmid: 20007864
references.citation: Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1377-84
references.pmid: 8616569
references.citation: Eur Rev Med Pharmacol Sci. 2012 Apr;16 Suppl 2:58-72
references.pmid: 22655484
references.citation: Nat Immunol. 2009 Sep;10(9):943-8
references.pmid: 19692995
references.citation: Orthopedics. 2012 Jun;35(6):e922-6
references.pmid: 22691668
references.citation: Clin Microbiol Rev. 2011 Apr;24(2):351-76
references.pmid: 21482729
references.citation: Eur J Immunol. 2012 Jan;42(1):147-57
references.pmid: 22215422
references.citation: Infect Immun. 2008 Jun;76(6):2333-40
references.pmid: 18347040
references.citation: J Exp Med. 2011 Jul 4;208(7):1339-50
references.pmid: 21727191
references.citation: Cell Microbiol. 2009 Aug;11(8):1151-9
references.pmid: 19388905
references.citation: J Infect Dis. 2005 Oct 1;192(7):1201-9
references.pmid: 16136463
references.citation: Clin Orthop Relat Res. 2007 Jul;460:39-49
references.pmid: 17438468
references.citation: Int J Tuberc Lung Dis. 2003 Dec;7(12):1178-85
references.pmid: 14677893
references.citation: Clin Infect Dis. 2010 May 15;50 Suppl 3:S223-30
references.pmid: 20397952
references.citation: PLoS One. 2009;4(1):e4228
references.pmid: 19156215
references.citation: J Bone Joint Surg Br. 2010 Jul;92(7):905-13
references.pmid: 20595106
references.citation: Am J Pathol. 2009 Jun;174(6):2211-24
references.pmid: 19435796
references.citation: Immunology. 2002 Mar;105(3):325-35
references.pmid: 11918694
references.citation: J Infect Dis. 2012 May 15;205 Suppl 2:S316-24
references.pmid: 22448014