Mice over-expressing CC chemokine ligand (CCL) 2 in the lung exhibit increased protective immunity to infection with M. bovis BCG

Rationale: The acute phase of mycobacterial lung infection is characterized by a nearly exponential outgrowth of mycobacteria within the alveolar airspace and lung parenchymal tissue, suggestive of an insufficient early protective immunity against mycobacterial challenge.

Objectives: In the current study, we questioned whether CCL2 over-expressing mice exhibiting an increased mononuclear phagocyte subset expansion within distal airspaces would demonstrate improved protective immunity to infection with Mycobacterium bovis Bacille Calmette-Guérin (M. bovis BCG).

Measurements and Main Results: CCL2 over-expressing and wild-type mice were infected with M. bovis BCG and subsequently analyzed for lung mononuclear phagocyte subset recruitment, lung granuloma formation and mycobacterial loads in BAL cells, lung parenchymal tissue and lung draining lymph nodes. CCL2 over-expressing mice infected with M. bovis BCG demonstrated significantly increased numbers of alveolar and lung macrophages, dendritic cells, and exudate mononuclear phagocytes both in BAL fluids and lung parenchymal tissue together with significantly decreased mycobacterial loads in their lungs when compared to wild-type mice. Moreover, an accelerated lung granuloma formation and resolution was noted in CCL2 over-expressing mice compared to controls at day 14 up until day 56 post-infection. In addition, CCL2 over-expressing mice demonstrated an increased trafficking of mycobacteria-loaded DC into lung draining lymph nodes, a process found to be independent of engagement of chemokine receptor CX3CR1.

Conclusions: The data of the current study support the concept that increased CCL2-dependent mononuclear phagocyte recruitment may improve lung protective immunity to mycobacterial infections.