CD43 is required for optimal growth inhibition of Mycobacterium tuberculosis in macrophages and in mice.
We explored the role of macrophage (Mphi) CD43, a transmembrane glycoprotein, in the pathogenesis of Mycobacterium tuberculosis. Using gene-deleted mice (CD43-/-), we assessed the association of the bacterium with distinct populations of Mphi and found that CD43-/- Mphi bound less M. tuberculosis than CD43+/+ Mphi. Increased infective doses did not abrogate this difference. However, reduced association due to the absence of CD43 could be overcome by serum components. Mphi from heterozygote mice, which express 50% of wild-type CD43, bound more bacteria than CD43-/- but less than CD43+/+, proving that the gene dose of CD43 correlates with binding of M. tuberculosis. Furthermore, the reduced ability of CD43-/- Mphi to bind bacteria was restricted to mycobacterial species. We also found that the survival and replication of M. tuberculosis within Mphi was enhanced significantly in the absence of CD43, making this the first demonstration that the mechanism of mycobacterial entry influences its subsequent growth. Most importantly, we show here that the absence of CD43 in mice aerogenically infected with M. tuberculosis results in an increased bacterial load during both the acute and chronic stages of infection and more rapid development of granulomas, with greater lung involvement and distinctive cellularity.
Randhawa
April K
AK
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Ziltener
Hermann J
HJ
Merzaban
Jasmeen S
JS
Stokes
Richard W
RW
D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001422:Bacterial Adhesion / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002908:Chronic Disease; D018628:Gene Dosage; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016130:Immunophenotyping; D051917:Leukosialin; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity; D009895:Opsonin Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D015703:Antigens, CD; D006131:Growth Inhibitors; D051917:Leukosialin; D009895:Opsonin Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse