Mycobacteria and human autoimmune disease: direct evidence of cross-reactivity between human lactoferrin and the 65-kilodalton protein of tubercle and leprosy bacilli.
We document here by Western immunoblotting and immunogold ultracytochemistry that polyclonal antibodies against human lactoferrin (Lf) bind to tubercle and leprosy bacilli. In situ immunogold labeling of Mycobacterium leprae (present in armadillo liver and in human skin) and of Mycobacterium tuberculosis indicated that receptors for anti-Lf antibodies were present both on the cytoplasm and on the envelope of the bacilli. We found by immunoblotting that the 65-kDa heat shock protein is the major component of M. leprae and M. tuberculosis that is responsible for the binding of the anti-Lf probe. Furthermore, we show that anti-Lf immunoglobulin G eluted from the nitrocellulose-transferred mycobacterial 65-kDa protein band did bind back to Lf. Ultracytochemistry of biopsy samples of human lepromas showed that dead or severely damaged M. leprae was strongly marked by the anti-Lf antibodies; a similar pattern of immunogold marking was observed on M. leprae when antibodies against the 65-kDa mycobacterial protein were used. Our results offer direct evidence that the 65-kDa protein of leprosy and tubercle bacilli is recognized with specificity by antibodies against the human protein Lf. The Lf-65-kDa protein antigenic cross-reactivity may contribute to the formation of autoantibodies and immune complexes as well as to other autoimmune events that are frequent in tuberculosis and leprosy. Our immunocytochemical data also suggest that the cross-reactivity may persist for some time after the death of mycobacteria in infected hosts.
Esaguy
N
N
Center for Experimental Cytology (INIC), University of Porto, Portugal.
Aguas
A P
AP
van Embden
J D
JD
Silva
M T
MT
D000818:Animals; D000918:Antibody Specificity; D001135:Armadillos; D001327:Autoimmune Diseases / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D003429:Cross Reactions; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000276:immunology*; D015440:Leprosy, Lepromatous / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000648:ultrastructure; D008970:Molecular Weight; D009166:Mycobacterium leprae / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000648:ultrastructure; D012867:Skin / Q000276:immunology / Q000648:ultrastructure
D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D007781:Lactoferrin