Proinflammatory polarization of monocytes by particulate air pollutants is mediated by induction of trained immunity in pediatric asthma.

Mar 20, 2023

Experts: Hesam Movassagh,Mary Prunicki,Abhinav Kaushik,Xiaoying Zhou,Diane Dunham,Eric M Smith,Ziyuan He,German R Aleman Muench,Minyi Shi,Annika K Weimer,Shu Cao,Sandra Andorf,Amir Feizi,Michael P Snyder,Pejman Soroosh,Elizabeth D Mellins,Kari C Nadeau

The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM ) are associated with alterations in circulating monocytes in children with or without asthma.
Monocyte phenotyping was performed by cytometry time-of-flight (CyTOF). Cytokines were measured using cytomtric bead array and Luminex assay. ChIP-Seq was utilized to address histone modifications in monocytes.
Increased exposure to ambient PM was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by the upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or lipopolysaccharide. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes.
The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

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ABOUT THE EXPERTS

Hesam Movassagh,Mary Prunicki,Abhinav Kaushik,Xiaoying Zhou,Diane Dunham,Eric M Smith,Ziyuan He,German R Aleman Muench,Minyi Shi,Annika K Weimer,Shu Cao,Sandra Andorf,Amir Feizi,Michael P Snyder,Pejman Soroosh,Elizabeth D Mellins,Kari C Nadeau

Hesam Movassagh

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Mary Prunicki

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Abhinav Kaushik

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Xiaoying Zhou

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Diane Dunham

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Eric M Smith

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Ziyuan He

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

German R Aleman Muench

Janssen Research & Development, LLC, San Diego, California, USA.

Minyi Shi

Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, California, USA.

Annika K Weimer

Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, California, USA.

Shu Cao

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Sandra Andorf

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Divisions of Biomedical Informatics and Allergy & Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA.

Amir Feizi

OMass Therapeutics, Oxford, UK.

Michael P Snyder

Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, California, USA.

Pejman Soroosh

Janssen Research & Development, LLC, San Diego, California, USA.

Elizabeth D Mellins

Department of Pediatrics, Stanford Program in Immunology, Stanford University School of Medicine, Stanford, California, USA.

Kari C Nadeau

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, California, USA.