TY - JOUR
T1 - Susceptibility to tuberculosis
T2 - Composition of tuberculous granulomas in Thorbecke and outbred New Zealand White rabbits
AU - Mendez, Susana
AU - Hatem, Christine L.
AU - Kesavan, Anup K.
AU - Lopez-Molina, Javier
AU - Pitt, M. Louise M.
AU - Dannenberg, Arthur M.
AU - Manabe, Yukari C.
N1 - Funding Information:
We would like to acknowledge the excellent animal care provided by Dr. Doris Hughes, Mike Manion, and Rob Bergman at George Washington University Medical Center. We are also grateful for scientific advice from Dr. Padmini Salgame & William Bishai, and technical support from Sandeep Tyagi. This work was supported by funding from the National Institutes of Health (1R01 HL71554 and NIAID-DMID Contract 03-09).
PY - 2008/3/15
Y1 - 2008/3/15
N2 - We sought to characterize the lung cellular immune responses to inhaled Mycobacterium tuberculosis (Mtb) of the susceptible inbred Thorbecke rabbit (the genomically sequenced strain, now unavailable) and compare it to outbred, Mtb-resistant, New Zealand White rabbits. Using Mtb CDC1551, we confirmed that the inbred rabbits allowed establishment of infection with this low virulence strain, compared to poor establishment in outbred rabbits. With a more virulent strain, Mtb Erdman, that establishes infection well in both rabbit strains, we analyzed granulomas from rabbit lungs 5 weeks after aerosol infection. The lung granulomas of inbred rabbits had significantly higher frequencies of cells expressing MHC Class II and CD11b, and lower frequencies of CD8+ T cells than the outbred controls. Macrophage-sized cells expressing MHC Class II in inbred rabbit granulomas showed significantly decreased intensity of expression, suggesting impaired maturation. Although the inbred dermal tuberculin reactions were decreased, the in vitro IFN-γ mRNA responses of hilar node lymphocytes to tuberculin were higher than those of outbred rabbits. Further delineation of the outbred rabbit's resistant immune response to Mtb infection is warranted.
AB - We sought to characterize the lung cellular immune responses to inhaled Mycobacterium tuberculosis (Mtb) of the susceptible inbred Thorbecke rabbit (the genomically sequenced strain, now unavailable) and compare it to outbred, Mtb-resistant, New Zealand White rabbits. Using Mtb CDC1551, we confirmed that the inbred rabbits allowed establishment of infection with this low virulence strain, compared to poor establishment in outbred rabbits. With a more virulent strain, Mtb Erdman, that establishes infection well in both rabbit strains, we analyzed granulomas from rabbit lungs 5 weeks after aerosol infection. The lung granulomas of inbred rabbits had significantly higher frequencies of cells expressing MHC Class II and CD11b, and lower frequencies of CD8+ T cells than the outbred controls. Macrophage-sized cells expressing MHC Class II in inbred rabbit granulomas showed significantly decreased intensity of expression, suggesting impaired maturation. Although the inbred dermal tuberculin reactions were decreased, the in vitro IFN-γ mRNA responses of hilar node lymphocytes to tuberculin were higher than those of outbred rabbits. Further delineation of the outbred rabbit's resistant immune response to Mtb infection is warranted.
KW - Animal model
KW - Dendritic cell
KW - Host susceptibility
KW - Rabbit
KW - Tuberculosis
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U2 - 10.1016/j.vetimm.2007.11.006
DO - 10.1016/j.vetimm.2007.11.006
M3 - Article
C2 - 18155300
AN - SCOPUS:39549094210
SN - 0165-2427
VL - 122
SP - 167
EP - 174
JO - Veterinary Immunology and Immunopathology
JF - Veterinary Immunology and Immunopathology
IS - 1-2
ER -