Logo of iaiPermissionsJournals.ASM.orgJournalIAI ArticleJournal InfoAuthorsReviewers
Infect Immun. 1996 Apr; 64(4): 1400–1406.
PMCID: PMC173932

Mycobacterium tuberculosis invades and replicates within type II alveolar cells.


Although Mycobacterium tuberculosis is assumed to infect primarily alveolar macrophages after being aspirated into the lung in aerosol form, it is plausible to hypothesize that M. tuberculosis can come in contact with alveolar epithelial cells upon arrival into the alveolar space. Therefore, as a first step toward investigation of the interaction between M. tuberculosis and alveolar epithelial cells, we examined the ability of M. tuberculosis to bind to and invade alveolar epithelial cells in vitro. The H37Rv and H37Ra strains of M. tuberculosis were cultured to mid-log phase and used in both adherence and invasion assays. The A549 human type II alveolar cell line was cultured to confluence in RPMI 1640 supplemented with 5% fetal bovine serum, L-glutamine, and nonessential amino acids. H37Rv was more efficient in entering A549 cells than H37Ra, Mycobacterium avium, and Escherichia coli Hb101, and nonpiliated strain (4.7% +/- 1.0% of the initial inoculum in 2 h compared with 3.1% +/- 0.8%, 2.1% +/- 0.9%, and 0.03% +/- 0.0%, respectively). The invasion was more efficient at 37 degrees C than 30 degrees C (4.7% +/- 1.0% compared with 2.3% +/- 0.8%). H37Rv and H37Ra were both capable of multiplying intracellularly at a similar ration over 4 days. Binding was inhibited up to 55.7% by anti-CD51 antibody (antivitronectin receptor), up to 55% with anti-CD29 antibody (beta(1) integrin), and 79% with both antibodies used together. Update of M. tuberculosis H37Rv was microtubule and microfilament dependent. It was inhibited by 6l.4% in the presence of 10 micron colchicine and by 72.3% in the presence of 3 micron cytochalasin D, suggesting two separate pathways for uptake. Our results show that M. tuberculosis is capable of invading type II alveolar epithelial cells and raise the possibility that invasion of alveolar epithelial cells is associated with the pathogenesis of lung infection.

Full Text

The Full Text of this article is available as a PDF (1.9M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bermudez LE, Young LS. Factors affecting invasion of HT-29 and HEp-2 epithelial cells by organisms of the Mycobacterium avium complex. Infect Immun. 1994 May;62(5):2021–2026. [PMC free article] [PubMed]
  • Bermudez LE, Young LS, Enkel H. Interaction of Mycobacterium avium complex with human macrophages: roles of membrane receptors and serum proteins. Infect Immun. 1991 May;59(5):1697–1702. [PMC free article] [PubMed]
  • Bloom BR, Murray CJ. Tuberculosis: commentary on a reemergent killer. Science. 1992 Aug 21;257(5073):1055–1064. [PubMed]
  • Byrd SR, Gelber R, Bermudez LE. Roles of soluble fibronectin and beta 1 integrin receptors in the binding of Mycobacterium leprae to nasal epithelial cells. Clin Immunol Immunopathol. 1993 Dec;69(3):266–271. [PubMed]
  • Crapo JD, Barry BE, Gehr P, Bachofen M, Weibel ER. Cell number and cell characteristics of the normal human lung. Am Rev Respir Dis. 1982 Jun;125(6):740–745. [PubMed]
  • Dannenberg AM., Jr Pathogenesis of pulmonary tuberculosis. Am Rev Respir Dis. 1982 Mar;125(3 Pt 2):25–29. [PubMed]
  • Filler SG, Swerdloff JN, Hobbs C, Luckett PM. Penetration and damage of endothelial cells by Candida albicans. Infect Immun. 1995 Mar;63(3):976–983. [PMC free article] [PubMed]
  • Finlay BB, Falkow S. Comparison of the invasion strategies used by Salmonella cholerae-suis, Shigella flexneri and Yersinia enterocolitica to enter cultured animal cells: endosome acidification is not required for bacterial invasion or intracellular replication. Biochimie. 1988 Aug;70(8):1089–1099. [PubMed]
  • Finlay BB, Ruschkowski S, Dedhar S. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. J Cell Sci. 1991 Jun;99(Pt 2):283–296. [PubMed]
  • Isberg RR, Falkow S. A single genetic locus encoded by Yersinia pseudotuberculosis permits invasion of cultured animal cells by Escherichia coli K-12. Nature. 1985 Sep 19;317(6034):262–264. [PubMed]
  • Isberg RR, Swain A, Falkow S. Analysis of expression and thermoregulation of the Yersinia pseudotuberculosis inv gene with hybrid proteins. Infect Immun. 1988 Aug;56(8):2133–2138. [PMC free article] [PubMed]
  • Adamson IY, Bowden DH. The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab Invest. 1974 Jan;30(1):35–42. [PubMed]
  • Mapother ME, Songer JG. In vitro interaction of Mycobacterium avium with intestinal epithelial cells. Infect Immun. 1984 Jul;45(1):67–73. [PMC free article] [PubMed]
  • Mette SA, Pilewski J, Buck CA, Albelda SM. Distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cells in vitro and in vivo. Am J Respir Cell Mol Biol. 1993 May;8(5):562–572. [PubMed]
  • Miller VL, Falkow S. Evidence for two genetic loci in Yersinia enterocolitica that can promote invasion of epithelial cells. Infect Immun. 1988 May;56(5):1242–1248. [PMC free article] [PubMed]
  • Oelschlaeger TA, Guerry P, Kopecko DJ. Unusual microtubule-dependent endocytosis mechanisms triggered by Campylobacter jejuni and Citrobacter freundii. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6884–6888. [PMC free article] [PubMed]
  • Racoosin EL, Swanson JA. Macrophage colony-stimulating factor (rM-CSF) stimulates pinocytosis in bone marrow-derived macrophages. J Exp Med. 1989 Nov 1;170(5):1635–1648. [PMC free article] [PubMed]
  • Ratliff TL, McCarthy R, Telle WB, Brown EJ. Purification of a mycobacterial adhesin for fibronectin. Infect Immun. 1993 May;61(5):1889–1894. [PMC free article] [PubMed]
  • Ratliff TL, Palmer JO, McGarr JA, Brown EJ. Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin. Cancer Res. 1987 Apr 1;47(7):1762–1766. [PubMed]
  • Schlesinger LS, Bellinger-Kawahara CG, Payne NR, Horwitz MA. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol. 1990 Apr 1;144(7):2771–2780. [PubMed]
  • SHEPARD CC. Phagocytosis by HeLa cells and their susceptibility to infection by human tubercle bacilli. Proc Soc Exp Biol Med. 1955 Nov;90(2):392–396. [PubMed]
  • Smith DW, Wiegeshaus E, Navalkar R, Grover AA. Host-parasite relationships in experimental airborne tuberculosis. I. Preliminary studies in BCG-vaccinated and nonvaccinated animals. J Bacteriol. 1966 Feb;91(2):718–724. [PMC free article] [PubMed]
  • Steinman RM, Mellman IS, Muller WA, Cohn ZA. Endocytosis and the recycling of plasma membrane. J Cell Biol. 1983 Jan;96(1):1–27. [PMC free article] [PubMed]
  • Wiegeshaus E, Balasubramanian V, Smith DW. Immunity to tuberculosis from the perspective of pathogenesis. Infect Immun. 1989 Dec;57(12):3671–3676. [PMC free article] [PubMed]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)


Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...