A macrophage invasion mechanism for mycobacteria implicating the extracellular domain of CD43.
We studied the role of CD43 (leukosialin/sialophorin), the negatively charged sialoglycoprotein of leukocytes, in the binding of mycobacteria to host cells. CD43-transfected HeLa cells bound Mycobacterium avium, but not Salmonella typhimurium or Shigella flexneri. Quantitative bacteriology showed that macrophages (M(phi)) from wild-type mice (CD43(+/+)) bound M. avium, Mycobacterium bovis (bacillus Calmette-Guérin), and Mycobacterium tuberculosis (strain H37Rv), whereas M(phi) from CD43 knockout mice (CD43(-/)-) did not. Fluorescence microscopy demonstrated that the associated M. avium had been ingested by the CD43(+/+) M(phi). The inability of CD43(-/)- M(phi) to bind M. avium could be restored by addition of galactoglycoprotein (Galgp), the extracellular mucin portion of CD43. The effect of Galgp is not due to opsonization of the bacteria, but required its interaction with the M(phi) other mucins had no effect. CD43 expression by the M(phi) was also required for optimal induction by M. avium of tumor necrosis factor (TNF)-alpha production, which likewise could be reconstituted by Galgp. In contrast, interleukin (IL)-10 production by M. avium-infected M(phi) was CD43 independent, demonstrating discordant regulation of TNF-alpha and IL-10. These findings describe a novel role of CD43 in promoting stable interaction of mycobacteria with receptors on the M(phi) enabling the cells to respond specifically with TNF-alpha production.
Fratazzi
C
C
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02111, USA.
Manjunath
N
N
Arbeit
R D
RD
Carini
C
C
Gerken
T A
TA
Ardman
B
B
Remold-O'Donnell
E
E
Remold
H G
HG
D000818:Animals; D015703:Antigens, CD; D001422:Bacterial Adhesion; D006367:HeLa Cells; D006801:Humans; D051917:Leukosialin; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000502:physiology; D009161:Mycobacterium / Q000502:physiology*; D010587:Phagocytosis; D012795:Sialoglycoproteins / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D051917:Leukosialin; D009077:Mucins; C465014:SPN protein, human; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D014409:Tumor Necrosis Factor-alpha