Mycobacterium tuberculosis persistence in various adipose depots of infected mice and the effect of anti-tubercular therapy

被引:31
作者
Agarwal, Pooja [1 ]
Khan, Shaheb R. [1 ]
Verma, Subash C. [1 ]
Beg, Muheeb [2 ]
Singh, Kavita [3 ]
Mitra, Kalyan [3 ,5 ]
Gaikwad, Anil N. [2 ,5 ]
Akhtar, Md. Sohail [4 ,5 ]
Krishnan, Manju Y. [1 ,5 ]
机构
[1] CSIR, Cent Drug Res Inst, Div Microbiol, Lucknow 226031, Uttar Pradesh, India
[2] CSIR, Cent Drug Res Inst, Div Pharmacol, Lucknow 226031, Uttar Pradesh, India
[3] CSIR, Cent Drug Res Inst, Sophisticated Analyt Instrument Facil, Electron Microscopy Lab, Lucknow 226031, Uttar Pradesh, India
[4] CSIR, Cent Drug Res Inst, Div Mol & Struct Biol, Lucknow 226031, Uttar Pradesh, India
[5] CSIR, Cent Drug Res Inst, Acad Sci & Innovat Res, Lucknow 226031, Uttar Pradesh, India
关键词
Mycobacterium tuberculosis; Adipocytes; Persistence; Mouse adipose depots; TISSUE; LATENCY; DRUG; DNA; DIFFERENTIATION; REACTIVATION; MORTALITY; PATIENT; CELLS;
D O I
10.1016/j.micinf.2014.04.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The adipocytes are one of the non-professional phagocytes postulated to be a haven for Mycobacterium tuberculosis during persistence in the human host. The adipocyte M. tuberculosis interaction data available to date are ex vivo. The present study was primarily aimed to investigate M. tuberculosis infection of adipocytes in course of infection of mouse model. Using primary murine adipocytes, the study first confirmed the infection and immunomodulation of natural adipocytes by M. tuberculosis. The bacilli could be isolated form visceral, subcutaneous, peri renal and mesenteric adipose depots of imrnunocompetent mice infected with M. tuberculosis intravenously. The bacilli could be isolated from adipocytes and the stromal vascular fraction, even though the numbers were significantly higher in the latter. The bacterial burden in the adipose depots was comparable to those in lungs in the early phase of infection. But with time, the burden in the adipose depots was either decreased or kept under control, despite the increasing burden in the lungs. Infected mice treated with standard anti tubercular drugs, despite effective elimination of bacterial loads in the lungs, continued to harbour M. tuberculosis in adipose depots at loads similar to untreated mice in the late infection phase. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:571 / 580
页数:10
相关论文
共 34 条
[1]   Extrapulmonary Locations of Mycobacterium tuberculosis DNA During Latent Infection [J].
Barrios-Payan, Jorge ;
Saqui-Salces, Milena ;
Jeyanathan, Mangalakumari ;
Alcantara-Vazquez, Avissai ;
Castanon-Arreola, Mauricio ;
Rook, Graham ;
Hernandez-Pando, Rogelio .
JOURNAL OF INFECTIOUS DISEASES, 2012, 206 (08) :1194-1205
[2]   Tuberculosis - Metabolism and respiration in the absence of growth [J].
Boshoff, HIM ;
Barry, CE .
NATURE REVIEWS MICROBIOLOGY, 2005, 3 (01) :70-80
[3]   Reversible Lipid Accumulation and Associated Division Arrest of Mycobacterium aviuum in Lipoprotein-Induced Foamy Macrophages May Resemble Key Events during Latency and Reactivation of Tuberculosis [J].
Caire-Braendli, Irene ;
Papadopoulos, Alexia ;
Malaga, Wladimir ;
Marais, David ;
Canaan, Stephane ;
Thilo, Lutz ;
de Chastellier, Chantal .
INFECTION AND IMMUNITY, 2014, 82 (02) :476-490
[4]   Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity [J].
Chackerian, AA ;
Alt, JM ;
Perera, TV ;
Dascher, CC ;
Behar, SM .
INFECTION AND IMMUNITY, 2002, 70 (08) :4501-4509
[5]   Lipid domains of mycobacteria studied with fluorescent molecular probes [J].
Christensen, H ;
Garton, NJ ;
Horobin, RW ;
Minnikin, DE ;
Barer, MR .
MOLECULAR MICROBIOLOGY, 1999, 31 (05) :1561-1572
[6]   CD271+ Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium tuberculosis [J].
Das, Bikul ;
Kashino, Suely S. ;
Pulu, Ista ;
Kalita, Deepjyoti ;
Swami, Vijay ;
Yeger, Herman ;
Felsher, Dean W. ;
Campos-Neto, Antonio .
SCIENCE TRANSLATIONAL MEDICINE, 2013, 5 (170)
[7]   Persister populations of Mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture media [J].
Dhillon, Jasvir ;
Fourie, P. Bernard ;
Mitchison, Denis A. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2014, 69 (02) :437-440
[8]   Global burden of tuberculosis - Estimated incidence, prevalence, and mortality by country [J].
Dye, C ;
Scheele, S ;
Dolin, P ;
Pathania, V ;
Raviglione, RC .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1999, 282 (07) :677-686
[9]   Lazy, Dynamic or Minimally Recrudescent? On the Elusive Nature and Location of the Mycobacterium Responsible for Latent Tuberculosis [J].
Ehlers, S. .
INFECTION, 2009, 37 (02) :87-95
[10]   Visceral adipose tissue specific persistence of Mycobacterium tuberculosis may be reason for the metabolic syndrome [J].
Erol, Adnan .
MEDICAL HYPOTHESES, 2008, 71 (02) :222-228