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Published on: January 7, 2019
RNAseq analysis demonstrates polarization state-dependent responses to ambient particulate matter in a particle
Timothy R Smyth1,2, Stephanie Brocke1,2, Weidong Wu3
1Curriculum in Toxicology & Environmental Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Abstract:
Macrophages are key innate immune cells which exist on a spectrum between pro-inflammatory (M1) and pro-resolutory (M2) states while retaining the ability to reprogram following exposure to new stimuli. Particulate matter (PM) exposure significantly alters macrophage function, leading to increasing respiratory infection morbidity and mortality. However, the influence of macrophage polarization on PM responses remains poorly understood. We hypothesized that human macrophages would demonstrate polarization state- and seasonality-specific responses to airborne PM collected from Xinxiang, China. CD14+CD16- monocytes were differentiated into macrophages and polarized using established methods with or without PM co-exposure followed by RNA sequencing (RNAseq). Macrophage expression profiles were primarily determined by inflammatory (M1) versus naive (M0) and alternative activation (M2), regardless of PM exposure. However, differential expression analysis using polarization state-specific reference groups uncovered distinct gene and pathway expression patterns. Directly polarized M0- > M1 macrophages exhibited the fewest unique differentially expressed genes (DEGs) but displayed similar pathway level activity to reprogrammed M2- > M1 cells. M2 macrophages showed the highest number of unique DEGs suggesting increased chemotactic pathway activity. Conversely, M0 cells exhibited greater expression of major inflammatory cytokines and chemokines. Although polarization state was the primary driver of gene and pathway responses, expression levels varied depending on PM collection dates and correlated strongly with individual PM components in M0 and M2 cells. These findings highlight the need to consider both particle seasonality and macrophage polarization state when studying PM's impact on macrophages as these factors may contribute to the negative health outcomes associated with PM exposure during respiratory infections.
Insights
Particulate matter (PM) exposure impacts macrophage polarization, influencing immune responses. Macrophage state and PM seasonality significantly alter gene expression, affecting respiratory health outcomes.
Area of Science:
- Immunology
- Environmental Health
- Cell Biology
Background:
- Macrophages are crucial innate immune cells with dynamic polarization states (M1/M1).
- Particulate matter (PM) exposure disrupts macrophage function, increasing respiratory illness severity.
- The role of macrophage polarization in PM responses is not well understood.
Purpose of the Study:
- To investigate human macrophage polarization- and seasonality-specific responses to airborne PM.
- To understand how PM exposure alters gene and pathway expression in different macrophage states.
Main Methods:
- Human monocytes (CD14+CD16-) were differentiated into macrophages.
- Macrophages were polarized (M0, M1, M2) with or without co-exposure to PM from Xinxiang, China.
- RNA sequencing (RNAseq) was performed to analyze gene expression profiles.
Main Results:
- Macrophage polarization state (M0, M1, M2) was the primary determinant of gene expression.
- M2 macrophages exhibited the most unique differentially expressed genes (DEGs), indicating increased chemotactic activity.
- PM seasonality and components influenced gene expression, particularly in M0 and M2 macrophages.
Conclusions:
- Macrophage polarization state significantly shapes responses to PM.
- PM's impact on macrophages is influenced by seasonality and specific particle components.
- Considering both polarization and seasonality is crucial for understanding PM's health effects.
