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MOLECULAR AND CELLULAR PATHOGENESIS

Invasion of the Brain and Chronic Central Nervous System Infection after Systemic Mycobacterium avium Complex Infection in Mice

Hsiu-Shan Wu, Peter Kolonoski, Yung Yee Chang, Luiz E. Bermudez
Hsiu-Shan Wu
Kuzell Institute for Arthritis and Infectious Disease, San Francisco, California
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Peter Kolonoski
Kuzell Institute for Arthritis and Infectious Disease, San Francisco, California
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Yung Yee Chang
Kuzell Institute for Arthritis and Infectious Disease, San Francisco, California
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Luiz E. Bermudez
Kuzell Institute for Arthritis and Infectious Disease, San Francisco, California
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DOI: 10.1128/IAI.68.5.2979-2984.2000
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  • Fig. 1.
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    Fig. 1.

    Mice were given 6 × 109 CFU ofM. avium 101 i.v. Four to 11 mice were used for blood culture and 3 to 7 mice were used for brain culture at each timepoint. Data are the mean CFU ± SEM. Mice had a significant increase in bacterial load in the brain within the first 2 months (P = 0.0058).

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    Fig. 2.

    Brain histopathology, showing intense infiltration of lymphocytes and macrophages in the optical chiasm 2 weeks after i.c. infection.

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    Fig. 3.

    Brain histopathology of mice receiving 3 × 108 CFU i.v. (A) At 1 month after inoculation, one nonnecrotizing granuloma was seen; HE strain. (B) Perivascular cuffing seen 2 months after inoculation. HE stain. (C) mild choroid plexus infiltration. HE stain. (D) acid-fast bacilli in the parenchyma of the choroid plexus. AFB stain. (E and F) At 4 months after infection there was cellular infiltration along the ventricle (E) (HE stain) and acid-fast bacilli were found in the lesion (F) (AFB stain). (G and H) At 6 months after inoculation, meningeal granuloma with foamy histiocytes was found (G) (HE stain) containing numerous acid-fast bacilli (H) (AFB stain). Magnifications: A and C, ×100; B, ×400; D, ×630; E and G, ×250; F and H, ×600.

Tables

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  • Table 1.

    Bacterial load in blood and brain after infection by different routes

    Time postinfectionSampleMean no. of bacteriaa (log CFU) (n = 3)
    107 CFU i.v.108 CFU i.v.109 CFU i.v.104 CFU i.c.
    2 hBlood4.885.47>6.24
    Brain0002.13
    1 dayBlood3.804.784.58
    Brain2.883.272.952.78
    7 daysBlood4.623.384.32
    Brain3.1513.884.013.381
    14 daysBlood2.562.654.88
    Brain4.301,23.9514.1814.011,2
    28 daysBlood<1.84.345.30
    Brain3.6514.561,2,34.691,24.511,2
    56 daysBlood2.364.043.71
    Brain2.874.681,2,34.691,23.40
    • ↵a 1, P < 0.05 compared with the number of bacteria in the brain at day 1; 2, P < 0.05 compared with the number of bacteria in the brain at day 7; 3, P < 0.05 compared with the number of bacteria in the brain at day 14.

  • Table 2.

    Number of bacteria in the brain of mice after i.c. inoculation

    Day after infectionNo. of bacteria/braina
    1.2 × 103 CFU1.2 × 104 CFU1.2 × 106 CFU
    101.75 × 1033.45 × 103
    44.2 × 102 a1.95 × 1033.3 × 104 a
    804.95 × 1036.38 × 104 a
    780NDb1.78 × 103
    • ↵a P < 0.05 compared with the number of bacteria in the brain at day 1.

    • ↵b ND, not done.

  • Table 3.

    Comparison of the number of M. avium in the brains of wild-type and CD18 KO mice after i.v. infectiona

    Day postinfection105 CFU/g of brain (mean ± SEM, n = 10)
    Wild typeCD18 KO
    11.2 ± 0.41.6 ± 0.2
    72.4 ± 0.32.7 ± 0.3
    143.5 ± 0.43.9 ± 0.1
    283.3 ± 0.64.0 ± 0.5
    • ↵a P > 0.05 for all the comparisons between number of bacteria in wild type and CD18 KO at each timepoint.

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Invasion of the Brain and Chronic Central Nervous System Infection after Systemic Mycobacterium avium Complex Infection in Mice
Hsiu-Shan Wu, Peter Kolonoski, Yung Yee Chang, Luiz E. Bermudez
Infection and Immunity May 2000, 68 (5) 2979-2984; DOI: 10.1128/IAI.68.5.2979-2984.2000

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Invasion of the Brain and Chronic Central Nervous System Infection after Systemic Mycobacterium avium Complex Infection in Mice
Hsiu-Shan Wu, Peter Kolonoski, Yung Yee Chang, Luiz E. Bermudez
Infection and Immunity May 2000, 68 (5) 2979-2984; DOI: 10.1128/IAI.68.5.2979-2984.2000
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KEYWORDS

brain
Central Nervous System Diseases
Mycobacterium avium Complex
tuberculosis

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