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

Abstract

SummaryM1 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.

Stimulation of bovine monocyte-derived macrophages with lipopolysaccharide, interferon-ɣ, Interleukin-4 or Interleukin-13 does not induce detectable changes in nitric oxide or arginase activity

“…The contradictory results reported by different groups using similar methodologies suggests that, in addition to species differences, there are strain and/or individual differences in macrophage responses to simulation. This has been substantiated by the findings of others; inbred strains of mice vary greatly in their ability to increase iNOS activity [16, 33]. Stimulation of bovine MDM with LPS and IFNγ resulted in 2-fold increases in NO activity when harvested from animals which were resistant to M. bovis but not from susceptible animals [23].…”

Protective immunity against tuberculosis: what does it look like and how do we find it?

“…The heterogeneity in phagocyte phenotype is also reflected in the relative balance of lymphocyte subsets in different granulomas in Mtb-infected macaques [ 38 ]. Finally, the manipulation of macrophage phenotypes in mice through the use of allergens, or the exploitation of different genetic backgrounds, impacts the ratio of M1/M2 type macrophage subsets and influences the bacterial burden [ 39 , 40 ].…”

Genetic Polymorphisms ofIL1B, IL6,andTNFαin a Chinese Han Population with Pulmonary Tuberculosis

“…It is reported that one-third of the world's population is infected with Mycobacterium tuberculosis ( MTB ); however, only 10% of the MTB infected population will develop TB disease during their lifetime. TB is mainly caused by MTB that primarily invades the lung phagocytes such as macrophages, neutrophils, monocytes, and dendritic cells [ 2 ]. In 90% of subjects infected with MTB (LTBI), the ensuing immune response arrests further the development of TB disease.…”