1. Diesel exhaust particulate matter impairs Toll-like receptor signaling and host defense against staphylococcal cutaneous infection in mice
- Author
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Madeeha Arooj, Abdur Rehman, Chang Lim Hyun, Asma Rafique, Hee-Kyoung Kang, Jin Won Hyun, and Young-Sang Koh
- Subjects
Diesel exhaust particulate matter ,PM2.5 ,Toll-like receptors ,Endocytosis ,S. aureus infection ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
Air pollution is an emerging cause of mortality, affecting nearly 5 million people each year. Exposure to diesel exhaust fine particulate matter (PM2.5) aggravates respiratory and skin conditions. However, its impact on the protective immunity of the skin remains poorly understood. This study aimed to investigate the underlying molecular mechanism for adverse effects of PM2.5 on the host protective immunity using in vitro cell and in vivo mouse model. Intracellular translocation of Toll-like receptor 9 (TLR9) and CpG-DNA internalization were assessed in dendritic cells without or with PM2.5 treatment using immunofluorescence staining. Cytokine and nitric oxide production were measured in dendritic cells and macrophages without or with PM2.5 treatment. NF-κB and MAPK signaling was determined using western blotting. Skin disease severity, bacterial loads, and cytokine production were assessed in cutaneous Staphylococcus aureus (S. aureus) infection mouse model. PM2.5 interfered with TLR9 activation by inhibiting both TLR9 trafficking to early endosomes and CpG-DNA internalization via clathrin-mediated endocytosis. In addition, exposure to PM2.5 inhibited various TLR-mediated nitric oxide and cytokine production as well as MAPK and NF-κB signaling. PM2.5 rendered mice more susceptible to staphylococcal skin infections. Our results suggest that exposure to PM impairs TLR signaling and dampens the host defense against staphylococcal skin infections. Our data provide a novel perspective into the impact of PM on protective immunity which is paramount to revealing air pollutant-mediated toxicity on the host immunity.
- Published
- 2023
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