Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin.
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.
Schreiber
Olivia
O
Department of Pulmonary Medicine, Research Center Borstel, Germany.
Steinwede
Kathrin
K
Ding
Nadine
N
Srivastava
Mrigank
M
Maus
Regina
R
Länger
Florian
F
Prokein
Jana
J
Ehlers
Stefan
S
Welte
Tobias
T
Gunn
Michael D
MD
Maus
Ulrich A
UA
D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D006099:Granuloma / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009163:Mycobacterium bovis; D010586:Phagocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2