The mechanism of this repolarization process is unknown. neoformans-infected lungs changed from an IL-4-dominated to an IFN-γ-dominated response over several weeks, with a corresponding shift in the overall macrophage polarization from M2 to M1 ( 26). neoformans infection using C57BL/6 mice ( 26). Collectively, these data indicate that M1/M2 macrophage polarization phenotypes are highly plastic to external signals, and interventions which therapeutically repolarize macrophages could be beneficial for treatment of cryptococcosis.Ī recent study demonstrated that the lung immune polarization environment changes over time in a model of chronic C. neoformans reflected the most recent polarizing condition, independent of previous polarization. Furthermore, the ability of sequentially stimulated macrophages to inhibit C. Switching IFN-γ- to IL-4-stimulating conditions, and vice versa, resulted in uniform changes in profiles of polarization marker genes consistent with the most recent cytokine environment. IFN-γ and IL-4 stimulation differentially induced complete M1 and M2 polarization, defined by differential expression of marker mRNA panels, surface marker expression, and tumor necrosis factor alpha (TNF-α) protein production. To further evaluate macrophage polarization plasticity, cytokine stimulatory conditions were established which fully polarized macrophages. neoformans and then with gamma interferon (IFN-γ) or IL-4 expressed mRNA polarization patterns similar to those stimulated with cytokines alone. neoformans-induced M1-like polarization state was plastic, as macrophages stimulated first with C. Coculture of macrophages with Cryptococcus neoformans resulted in development of a weak M1-like phenotype, with modestly increased inducible nitric oxide synthase (iNOS) but lacking interleukin 6 (IL-6) induction. To explore the ability of macrophages to change between polarization states, we conducted a series of experiments using in vitro macrophages. This could have been caused by repolarization of individual macrophages or by a replacement of M2-polarized cells by new M1-polarized cells. Overall, pulmonary macrophage polarization status changes over time during a cryptococcal infection. The outcome of cryptococcal pneumonia correlates with local macrophage polarization status, as M1 and M2 polarization marks protective and nonprotective responses, respectively.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |