Macrophage M1/M2 Polarization Dynamically Adapts to Changes in Cytokine Microenvironments in Cryptococcus neoformans Infection

Content Provider	Semantic Scholar
Author	Davis, Michael J. Tsang, Tiffany Qiu, Yafeng Dayrit, Jeremy K. Freij, Joudeh Bishara Huffnagle, Gary B. Olszewski, Michal A.
Copyright Year	2013
Abstract	The outcome of cryptococcal pneumonia correlates with local macrophage polarization status, as M1 and M2 polarization marks protective and nonprotective responses, respectively. Overall, pulmonary macrophage polarization status changes over time during a cryptococcal infection. This could have been caused by repolarization of individual macrophages or by a replacement of M2-polarized cells by new M1-polarized cells. To explore the ability of macrophages to change between polarization states, we conducted a series of experiments using in vitro macrophages. 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. The C. neoformans-induced M1-like polarization state was plastic, as macrophages stimulated first with C. neoformans and then with gamma interferon (IFN-γ) or IL-4 expressed mRNA polarization patterns similar to those stimulated with cytokines alone. To further evaluate macrophage polarization plasticity, cytokine stimulatory conditions were established which fully polarized macrophages. 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. 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. Furthermore, the ability of sequentially stimulated macrophages to inhibit C. neoformans reflected the most recent polarizing condition, independent of previous polarization. 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.
Starting Page	794
Ending Page	799
Page Count	6
File Format	PDF HTM / HTML
PubMed reference number	23781069
Alternate Webpage(s)	https://doi.org/10.1128/mBio.00264-13
DOI	10.1128/mbio.00264-13
Journal	mBio
Volume Number	4
Language	English
Access Restriction	Open
Subject Keyword	Biomarkers, Tumor Coculture Techniques Cryptococcus neoformans Ab:Titr:Pt:Ser:Qn Infection by Cryptococcus neoformans Interleukin-6 Interleukins Macrophages, Alveolar Necrosis Neoplasms Nitric Oxide Synthase Type II Phenotype Pneumocystis jiroveci pneumonia Recombinant Interferon-gamma cytokine
Content Type	Text
Resource Type	Article