Clinical and immunologic features of an atypical intracranial mycobacterium avium complex (MAC) infection compared with those of pulmonary MAC infections.
Members of the Mycobacterium avium complex (MAC) may cause chronic pulmonary infections in otherwise healthy elderly persons but rarely invade parts of the body outside of the lungs in immunocompetent hosts. We present a case of an isolated intracranial MAC infection in an apparently immunocompetent individual and review previous reports. We studied the T-cell and monocyte responses in healthy volunteers, individuals with a pulmonary MAC infection, and one individual with an isolated intracranial MAC infection. Genomic DNA from the individual with the brain MAC infection was studied for gamma interferon (IFN-gamma) receptor mutations. Individuals with localized pulmonary MAC infections showed increased activation of monocytes and enhanced monocyte and T-cell tumor necrosis factor alpha (TNF-alpha) production in response to lipopolysaccharide and MAC antigens but defects in T-cell IFN-gamma secretion. The individual with an intracranial MAC infection showed a lack of monocyte activation and deficiencies in both monocyte and T-cell TNF-alpha production and monocyte interleukin-12 (IL-12) production but had preserved T-cell IFN-gamma production. Mutations or deletions in the IFN-gamma receptor were not detected in the individual with the intracranial MAC infection. Our data suggest that distinct immune defects characterize two different manifestations of MAC infection. A relative defect in IFN-gamma production in response to MAC may predispose an individual to localized but partially controlled lung disease, whereas defects leading to reduced IL-12 and TNF-alpha production may allow the dissemination of MAC. Further studies delineating the potential role of TNF-alpha in limiting the spread of MAC outside the lung are warranted.
Sadek
Mouhannad
M
Clinical Sciences Division, Rm. 6271, 1 King's College Circle, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Yue
Feng Yun
FY
Lee
Erika Yue
EY
Gyenes
Gabor
G
Jones
R Brad
RB
Hoffstein
Victor
V
Munoz
David G
DG
Fong
Ignatius
I
Ostrowski
Mario
M
D006257:Head / Q000000981:diagnostic imaging; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D015269:Mycobacterium avium Complex / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology* / Q000503:physiopathology*; D011859:Radiography; D017471:Receptors, Interferon / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014390:Tuberculosis, Meningeal / Q000276:immunology* / Q000503:physiopathology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000503:physiopathology*; D000096743:Interferon gamma Receptor
D016898:Interferon-alpha; D007371:Interferon-gamma; D018664:Interleukin-12; D008070:Lipopolysaccharides; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor