Mycobacterium bovis BCG vaccine fails to protect protein-deficient guinea pigs against respiratory challenge with virulent Mycobacterium tuberculosis

Abstract

Specific-pathogen-free Hartley guinea pigs were maintained on isocaloric-purified diets either adequate (30%) or moderately deficient (10%) in protein. Half of each diet group was vaccinated with viable Mycobacterium bovis BCG. Six weeks later, all animals were challenged by the respiratory route with virulent Mycobacterium tuberculosis H37Rv. At intervals of 1, 2, and 3 weeks postchallenge, guinea pigs from each diet and vaccination group were skin tested with tuberculin and sacrificed. Protein deficiency resulted in loss of tuberculin hypersensitivity. Vaccination with M. bovis BCG protected control animals, as determined by significant reductions in the number of M. tuberculosis H37Rv organisms recovered from lungs, spleen, and bronchotracheal lymph nodes 2 and 3 weeks postchallenge. Based upon the same criteria, the degree of protection afforded protein-deficient animals by M. bovis BCG vaccine ranged from partial (spleen and lymph nodes) to none at all (lungs). Approximately the same numbers of tubercle bacilli were recovered from nonvaccinated guinea pigs in both diet groups. Protein deficiency appears to impair M. bovis BCG-induced immunity while not affecting primary pulmonary infection with virulent M. tuberculosis.

Vaccination with Mycobacterium bovis BCG affects the distribution of Fc receptor-bearing T lymphocytes in experimental pulmonary tuberculosis

“…tuberculosis H37Rv in the guinea pig model (2,12,13,21). Successful vaccination minimizes hematogenous dissemination of tubercle bacilli to distal organs such as the spleen, may modulate resulting in significant reductions in the mycobacterial load Ivith pulmonary in that organ (Table 1).…”

Proteasome inhibitor MG‐132 enhances the expression of interleukin‐6 in human umbilical vein endothelial cells: Involvement of MAP/ERK kinase

“…Proteasome is a multisubunit complex that degrades various cellular proteins, and the degradation in this complex requires a specific signal: attachment of a multiubiquitin chain to the target protein. It has been reported that protease inhibitors induce overexpression of factors such as heat‐shock proteins, 16 , 17 ATF3, GADD153 and MAD1; 18 however, regulation of cytokine production in vascular endothelial cells by the protease system has not been known.…”

Manipulation of immune responses to Mycobacterium bovis by vaccination with IL‐2‐ and IL‐18‐secreting recombinant bacillus Calmette Guerin

“…To prepare these suspensions, the bacterial cells were dispersed by sonication for 30 s and filtered through an 8 µm filter. The mice were infected via the respiratory route using an aerosol chamber that produces droplet nuclei of the size appropriate for entry into alveolar spaces 15 , 16 . The concentration of viable M. bovis in the nebulizer fluid was empirically adjusted to result in the inhalation and retention of approximately 10 viable organisms per mouse.…”