Immunomodulation of susceptibility to pneumococcal pneumonia infection in mouse lungs exposed to carbon nanoparticles via dysregulation of innate and adaptive immune responses

Mohammed, Afzaal Nadeem; Yadav, Niket; Kaur, Perminder; Jandarov, Roman; Yadav, Jagjit Singh

doi:10.1016/j.taap.2024.116820

Toxicology and Applied Pharmacology

2024

DOI: 10.1016/j.taap.2024.116820

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Immunomodulation of susceptibility to pneumococcal pneumonia infection in mouse lungs exposed to carbon nanoparticles via dysregulation of innate and adaptive immune responses

Afzaal Nadeem Mohammed,

Niket Yadav,

Perminder Kaur

et al.

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2024

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Carbon Nanotube Immunotoxicity in Alveolar Epithelial Type II Cells Is Mediated by Physical Contact-Independent Cell–Cell Interaction with Macrophages as Demonstrated in an Optimized Air–Liquid Interface (ALI) Coculture Model

Yadav,

Yadav

2024

Nanomaterials

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There is a need for the assessment of respiratory hazard potential and mode of action of carbon nanotubes (CNTs) before their approval for technological or medical applications. In CNT-exposed lungs, both alveolar macrophages (MФs), which phagocytose CNTs, and alveolar epithelial type II cells (AECII cells), which show tissue injury, are impacted but cell–cell interactions between them and the impacted mechanisms are unclear. To investigate this, we first optimized an air–liquid interface (ALI) transwell coculture of human AECII cell line A549 (upper chamber) and human monocyte cell line THP-1 derived macrophages (lower chamber) in a 12-well culture by exposing macrophages to CNTs at varying doses (5–60 ng/well) for 12–48 h and measuring the epithelial response markers for cell differentiation/maturation (proSP-C), proliferation (Ki-67), and inflammation (IL-1β). In optimal ALI epithelial-macrophage coculture (3:1 ratio), expression of Ki-67 in AECII cells showed dose dependence, peaking at 15 ng/well CNT dose; the Ki-67 and IL-1β responses were detectable within 12 h, peaking at 24–36 h in a time-course. Using the optimized ALI transwell coculture set up with and without macrophages, we demonstrated that direct interaction between CNTs and MФs, but not a physical cell–cell contact between MФ and AECII cells, was essential for inducing immunotoxicity (proliferative and inflammatory responses) in the AECII cells.

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Carbon Nanotube Immunotoxicity in Alveolar Epithelial Type II Cells Is Mediated by Physical Contact-Independent Cell–Cell Interaction with Macrophages as Demonstrated in an Optimized Air–Liquid Interface (ALI) Coculture Model

Yadav,

Yadav

2024

Nanomaterials

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Immunomodulation of susceptibility to pneumococcal pneumonia infection in mouse lungs exposed to carbon nanoparticles via dysregulation of innate and adaptive immune responses

Cited by 1 publication

References 67 publications

Carbon Nanotube Immunotoxicity in Alveolar Epithelial Type II Cells Is Mediated by Physical Contact-Independent Cell–Cell Interaction with Macrophages as Demonstrated in an Optimized Air–Liquid Interface (ALI) Coculture Model

Carbon Nanotube Immunotoxicity in Alveolar Epithelial Type II Cells Is Mediated by Physical Contact-Independent Cell–Cell Interaction with Macrophages as Demonstrated in an Optimized Air–Liquid Interface (ALI) Coculture Model

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