PMID- 18068491
OWN - NLM
STAT- MEDLINE
DCOM- 20080821
LR  - 20211020
IS  - 1472-9792 (Print)
IS  - 1873-281X (Electronic)
IS  - 1472-9792 (Linking)
VI  - 88
IP  - 3
DP  - 2008 May
TI  - The aerosol rabbit model of TB latency, reactivation and immune reconstitution 
      inflammatory syndrome.
PG  - 187-96
AB  - The large reservoir of human latent tuberculosis (TB) contributes to the global 
      success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test 
      whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary 
      human latent TB. The lung burden of infection peaked at 5 weeks after aerosol 
      infection followed by host containment of infection that was achieved in all 
      rabbits. One-third of rabbits had at least one caseous granuloma with culturable 
      bacilli at 36 weeks after infection suggesting persistent paucibacillary 
      infection. Corticosteroid-induced immunosuppression initiated after disease 
      containment resulted in reactivation of disease. Seventy-two percent of rabbits 
      had culturable bacilli in the right upper lung lobe homogenates compared to none 
      of the untreated controls. Discontinuation of dexamethasone led to predictable 
      lymphoid recovery, with a proportion of rabbits developing multicentric large 
      caseous granuloma. The development and severity of the immune reconstitution 
      inflammatory syndrome (IRIS) was dependent on the antigen load at the time of 
      immunosuppression and subsequent bacillary replication during 
      corticosteroid-induced immunosuppression. Clinically, many aspects were similar 
      to IRIS in severely immunosuppressed HIV-infected patients who have functional 
      restoration of T cells in response to effective (highly active) antiretroviral 
      therapy. This corticosteroid model is the only animal model of the IRIS. Further 
      study of the rabbit model of TB latency, reactivation and IRIS may be important 
      in understanding the immunopathogenesis of these poorly modeled states as well as 
      for improved diagnostics for specific stages of disease.
FAU - Manabe, Yukari C
AU  - Manabe YC
AD  - Center for Tuberculosis Research, Johns Hopkins University, 720 Rutland Street, 
      Rm 1147B, Baltimore, MD 21205, USA. ymanabe@jhmi.edu
FAU - Kesavan, Anup K
AU  - Kesavan AK
FAU - Lopez-Molina, Javier
AU  - Lopez-Molina J
FAU - Hatem, Christine L
AU  - Hatem CL
FAU - Brooks, Megan
AU  - Brooks M
FAU - Fujiwara, Ricardo
AU  - Fujiwara R
FAU - Hochstein, Karl
AU  - Hochstein K
FAU - Pitt, M Louise M
AU  - Pitt ML
FAU - Tufariello, Joann
AU  - Tufariello J
FAU - Chan, John
AU  - Chan J
FAU - McMurray, David N
AU  - McMurray DN
FAU - Bishai, William R
AU  - Bishai WR
FAU - Dannenberg, Arthur M Jr
AU  - Dannenberg AM Jr
FAU - Mendez, Susana
AU  - Mendez S
LA  - eng
GR  - R01 HL071554/HL/NHLBI NIH HHS/United States
GR  - 1R01 HL71554/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071218
PL  - Scotland
TA  - Tuberculosis (Edinb)
JT  - Tuberculosis (Edinburgh, Scotland)
JID - 100971555
RN  - 0 (Aerosols)
RN  - 0 (Glucocorticoids)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Aerosols
MH  - Animals
MH  - Dexamethasone/toxicity
MH  - *Disease Models, Animal
MH  - Flow Cytometry
MH  - Glucocorticoids/toxicity
MH  - Immune Reconstitution Inflammatory Syndrome/chemically 
      induced/immunology/*microbiology
MH  - Lung/pathology
MH  - Mycobacterium tuberculosis/growth & development/isolation & 
      purification/*pathogenicity
MH  - Organ Size
MH  - Rabbits
MH  - Tuberculoma/microbiology/pathology
MH  - Tuberculosis, Pulmonary/immunology/*microbiology/pathology
PMC - PMC4477206
MID - NIHMS50247
EDAT- 2007/12/11 09:00
MHDA- 2008/08/22 09:00
PMCR- 2015/06/23
CRDT- 2007/12/11 09:00
PHST- 2006/08/08 00:00 [received]
PHST- 2007/10/27 00:00 [revised]
PHST- 2007/10/29 00:00 [accepted]
PHST- 2007/12/11 09:00 [pubmed]
PHST- 2008/08/22 09:00 [medline]
PHST- 2007/12/11 09:00 [entrez]
PHST- 2015/06/23 00:00 [pmc-release]
AID - S1472-9792(07)00131-X [pii]
AID - 10.1016/j.tube.2007.10.006 [doi]
PST - ppublish
SO  - Tuberculosis (Edinb). 2008 May;88(3):187-96. doi: 10.1016/j.tube.2007.10.006. 
      Epub 2007 Dec 18.