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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus
1Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing Medical University, Chongqing, China.
Background:
Regulatory T cells (Treg cells), which are essential for regulation of immune response to respiratory syncytial virus (RSV) infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified.
Methods:
Female BALB/c mice (aged 3 weeks) were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH(2)O) from 1 d post infection (pi). Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF) were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR), pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA) challenge was used to induce AHR after RSV infection.
Results:
The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under OVA challenge.
Conclusions:
After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.
Insights
Antibiotic treatment after respiratory syncytial virus (RSV) infection reduced beneficial pharyngeal bacteria, leading to increased airway hyperresponsiveness (AHR) and decreased regulatory T cells (Treg cells). This suggests a link between gut microbiota and immune responses.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Regulatory T cells (Treg cells) are crucial for managing immune responses to respiratory syncytial virus (RSV) infection.
- Pharyngeal commensal bacteria, like Streptococcus, promote Treg cells.
- The impact of antibiotic-induced disruption of pharyngeal microflora on airway responsiveness and immune responses post-RSV infection remains unclear.
Purpose of the Study:
- To investigate the effects of antibiotic treatment on pharyngeal microflora.
- To assess the impact of antibiotic treatment on airway responsiveness and immune responses after RSV infection in mice.
Main Methods:
- Female BALB/c mice were infected with RSV and treated with oral antibiotics or water.
- Pharyngeal microflora changes were analyzed.
- Airway hyperresponsiveness (AHR), pulmonary histopathology, and Treg cell responses were evaluated.
- Gene expression (Foxp3) and cytokine levels (IL-10, TGF-β1) were measured.
Main Results:
- Antibiotic treatment effectively cleared Streptococcus from the pharynx.
- RSV-infected mice treated with antibiotics exhibited increased AHR.
- A decrease in pulmonary Treg cells, Foxp3 mRNA, and TGF-β1 was observed in antibiotic-treated mice.
- Similar effects were noted in ovalbumin (OVA)-induced AHR models.
Conclusions:
- Antibiotic treatment following RSV infection eradicates key pharyngeal commensal bacteria.
- This disruption may lead to increased airway hyperresponsiveness (AHR).
- Antibiotic treatment is associated with a reduction in pulmonary Treg cells after RSV infection.
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