Osteopontin expression correlates with clinical outcome in patients with mycobacterial infection.
Osteopontin (OPN) is a protein that is expressed in chronic inflammatory diseases including tuberculosis, and its deficiency predisposes to more severe mycobacterial infections in mice. However, no reports have identified altered OPN expression in, or correlated these alterations to, infections in humans. The data presented herein identify alterations in the tissue expression of OPN protein and describe an inverse correlation between these levels and disease progression after inoculation of Mycobacterium bovis bacillus Calmette-Guérin vaccine in humans. Patients with regional adenitis and good clinical outcomes had abundant OPN in infected lymph nodes. This pattern of OPN accumulation was also observed in patients infected by M. avium-intracellulare. In contrast, patients with disseminated infection and histologically ill-defined granulomas had no significant osteopontin accumulation in infected lymph nodes; these patients had either deficiencies in the interferon-gamma receptor 1 or idiopathic immune defects. The level of OPN protein expression was inversely correlated with disseminated infection and, of particular interest, with death of the patient. We conclude that osteopontin expression correlates with an effective immune and inflammatory response when humans are challenged by a mycobacterial infection and that osteopontin contributes to human resistance against mycobacteria.
Nau
G J
GJ
Whitehead Institute for Biomedical Research and Department of Biology, Cambridge 02142, USA.
Chupp
G L
GL
Emile
J F
JF
Jouanguy
E
E
Berman
J S
JS
Casanova
J L
JL
Young
R A
RA
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008199:Lymphadenitis / Q000378:metabolism / Q000473:pathology; D008297:Male; D009163:Mycobacterium bovis; D053495:Osteopontin; D017471:Receptors, Interferon / Q000172:deficiency; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D000096743:Interferon gamma Receptor; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053495:Osteopontin; D017471:Receptors, Interferon; D012795:Sialoglycoproteins; D000096743:Interferon gamma Receptor; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C506895:SPP1 protein, human