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Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin.

Publication ,  Journal Article
Schreiber, O; Steinwede, K; Ding, N; Srivastava, M; Maus, R; Länger, F; Prokein, J; Ehlers, S; Welte, T; Gunn, MD; Maus, UA
Published in: J Infect Dis
October 1, 2008

BACKGROUND: The acute phase of mycobacterial lung infection is characterized by a nearly exponential outgrowth of mycobacteria in the alveolar airspace and lung parenchymal tissue, suggesting insufficient early protective immunity against mycobacterial challenge. In the current study, we tested the hypothesis that a CC chemokine ligand 2 (CCL2)-dependent increased mononuclear phagocyte subset accumulation in distal airspaces would improve the lungs' protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin (hereafter, "M. bovis BCG"). METHODS: Wild-type mice and CCL2-overexpressing mice that exhibited increased pools of alveolar and lung mononuclear phagocytes-due to the lung-specific overexpression of human CCL2 in type-II alveolar epithelial cells-were infected intratracheally with M. bovis BCG and the developing lung inflammatory response was analyzed. RESULTS: CCL2-overexpressing mice demonstrated significantly decreased mycobacterial loads in the bronchoalveolar space, lung parenchymal tissue, and spleen compared with wild-type mice, when both groups of mice were infected with M. bovis BCG. Moreover, in M. bovis BCG-infected mice, later-developing, accelerated resolution of lung granuloma formation was noted, particularly in CCL2-overexpressing mice as compared with wild-type mice. In addition, CCL2-overexpressing mice demonstrated an increased trafficking of mycobacteria-loaded dendritic cells towards lung-draining lymph nodes that was found to coincide with increased mycobacterial loads in this compartment. CONCLUSIONS: The data of the current study suggest that CCL2-dependent amplification of endogenous host-defense programs in the lung may improve the lungs' protective immunity against mycobacterial infections.

Duke Scholars

Published In

J Infect Dis

DOI

ISSN

0022-1899

Publication Date

October 1, 2008

Volume

198

Issue

7

Start / End Page

1044 / 1054

Location

United States

Related Subject Headings

  • Tuberculosis
  • Phagocytes
  • Mycobacterium bovis
  • Microbiology
  • Mice, Transgenic
  • Mice, Inbred BALB C
  • Mice
  • Lymph Nodes
  • Lung
  • Granuloma
 

Citation

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Schreiber, O., Steinwede, K., Ding, N., Srivastava, M., Maus, R., Länger, F., … Maus, U. A. (2008). Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin. J Infect Dis, 198(7), 1044–1054. https://doi.org/10.1086/591501
Schreiber, Olivia, Kathrin Steinwede, Nadine Ding, Mrigank Srivastava, Regina Maus, Florian Länger, Jana Prokein, et al. “Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin.J Infect Dis 198, no. 7 (October 1, 2008): 1044–54. https://doi.org/10.1086/591501.
Schreiber O, Steinwede K, Ding N, Srivastava M, Maus R, Länger F, et al. Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin. J Infect Dis. 2008 Oct 1;198(7):1044–54.
Schreiber, Olivia, et al. “Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin.J Infect Dis, vol. 198, no. 7, Oct. 2008, pp. 1044–54. Pubmed, doi:10.1086/591501.
Schreiber O, Steinwede K, Ding N, Srivastava M, Maus R, Länger F, Prokein J, Ehlers S, Welte T, Gunn MD, Maus UA. Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin. J Infect Dis. 2008 Oct 1;198(7):1044–1054.
Journal cover image

Published In

J Infect Dis

DOI

ISSN

0022-1899

Publication Date

October 1, 2008

Volume

198

Issue

7

Start / End Page

1044 / 1054

Location

United States

Related Subject Headings

  • Tuberculosis
  • Phagocytes
  • Mycobacterium bovis
  • Microbiology
  • Mice, Transgenic
  • Mice, Inbred BALB C
  • Mice
  • Lymph Nodes
  • Lung
  • Granuloma