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Updated: Sep 23, 2025
Examining the Role of Nasopharyngeal-associated Lymphoreticular Tissue NALT in Mouse Responses to Vaccines
Published on: August 1, 2012
TLR3 and TLR7/8 agonists improve immunization outcome in nicotine exposed mice through different mechanisms
Mahyar Nouri-Shirazi1, Elisabeth Guinet1
1Florida Atlantic University, Charles E. Schmidt College of Medicine, Integrated Medical Science Department, Florida Atlantic University, 777 Glades Road, PO Box 3091, Boca Raton, Florida, 33431, USA.
Abstract:
It is known that cigarette smoke compromises the immune system and increases the risk of vaccine-preventable diseases. We reported that nicotine, the immunosuppressive component of cigarette smoke, disrupts the functional properties of DC and DC crosstalk with NK cells, which is pivotal in the initiation of immune responses to vaccines. We also showed that select TLR agonists could reduce the degrading effects of nicotine on DC-NK mediated immune responses in vitro. In this study, we further investigated the magnitude and mechanism of immune responses to a protein antigen formulated with alum or TLR agonists using WT, NK-depleted, and IFN-γ deficient mice exposed to nicotine. We found that R848 followed by Poly(I:C) acted as the most effective adjuvants to increase the percentage and number of IFN-γ-producing effector NK cells in the lymph nodes of immunized mice. In addition, we observed that the protein antigen formulated with Poly(I:C) or R848 improved the antigen-specific immune response in nicotine-exposed mice through NK-independent and -dependent mechanisms, respectively. These findings extend our understanding of the hyporesponsiveness of smokers to vaccines and provides the means to increase the efficacy of vaccines in this large population.
Insights
Nicotine from cigarette smoke weakens immune responses to vaccines. Certain Toll-like receptor (TLR) agonists can enhance vaccine efficacy in nicotine-exposed individuals by boosting NK cell activity.
Area of Science:
- Immunology
- Vaccinology
- Toxicology
Background:
- Cigarette smoke impairs immune function, increasing susceptibility to vaccine-preventable diseases.
- Nicotine, a key component of smoke, disrupts dendritic cell (DC) function and DC-NK cell interactions crucial for vaccine immunity.
- Previous in vitro studies indicated Toll-like receptor (TLR) agonists may counteract nicotine's immunosuppressive effects on DC-NK cell responses.
Purpose of the Study:
- To investigate the impact of nicotine exposure on immune responses to a protein antigen formulated with alum or TLR agonists in vivo.
- To elucidate the mechanisms underlying vaccine hyporesponsiveness in nicotine-exposed individuals.
- To identify effective adjuvants for improving vaccine efficacy in smokers.
Main Methods:
- Utilized wild-type (WT), NK-depleted, and interferon-gamma (IFN-γ) deficient mice exposed to nicotine.
- Administered a protein antigen formulated with alum, R848, or Poly(I:C) adjuvants.
- Assessed immune responses, including the percentage and number of IFN-γ-producing effector NK cells in lymph nodes.
Main Results:
- R848 followed by Poly(I:C) demonstrated the most significant enhancement of IFN-γ-producing effector NK cells in immunized mice.
- Protein antigen formulated with Poly(I:C) or R848 improved antigen-specific immune responses in nicotine-exposed mice.
- These improvements occurred via NK-independent mechanisms for Poly(I:C) and NK-dependent mechanisms for R848.
Conclusions:
- Findings provide insights into the mechanisms of vaccine hyporesponsiveness in smokers.
- Specific TLR agonists, particularly R848 and Poly(I:C), can enhance vaccine efficacy in nicotine-exposed populations.
- This research offers potential strategies to improve vaccine effectiveness in smokers.
