Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis-infected hosts.

Abstract

M1 macrophages are more effective in the induction of the inflammatory response and clearance of Mycobacterium tuberculosis than M2 macrophages. Infected C57BL/6 mice generate a stronger cellular immune response compared with BALB/c mice. We hypothesized that infected C57BL/6 mice would exhibit a higher frequency and function of M1 macrophages than infected BALB/c mice. Our findings show a higher ratio of macrophages to M2 macrophages in the lungs of chronically infected C57BL/6 mice compared with BALB/c mice. However, there was no difference in the functional ability of M1 and M2 macrophages for the two strains in vitro. In vivo, a deleterious role for M2 macrophages was confirmed by M2 cell transfer, which rendered the infected C57BL/6, but not the BALB/c mice, more susceptible and resulted in mild lung inflammation compared with C57BL/6 mice that did not undergo cell transfer. M1 cell transfer induced a higher inflammatory response, although not protective, in infected BALB/c mice compared with their counterparts that did not undergo cell transfer. These findings demonstrate that an inflammation mediated by M1 macrophages may not induce bacterial tolerance because protection depends on the host genetic background, which drives the magnitude of the inflammatory response against M. tuberculosis in the pulmonary microenvironment. The contribution of our findings is that although M1 macrophage is an effector leucocyte with microbicidal machinery, its dominant role depends on the balance of M1 and M2 subsets, which is driven by the host genetic background.

DOI: 10.1111/imm.12591

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@article{Bertolini2016GeneticBA, title={Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis-infected hosts.}, author={Tha{\'i}s Barboza Bertolini and Alexandre Ignacio de Souza and Ana Fl{\'a}via Gembre and Annie Rocio Pi{\~n}eros and Rafael de Queiroz Prado and Jo{\~a}o Santana da Silva and Leandra N{\'a}ira Zambelli Ramalho and V{\^a}nia Luiza Deperon Bonato}, journal={Immunology}, year={2016}, volume={148 1}, pages={102-13} }