Abstract Title

IL-17A(+) CD4(+) T-Cells and Neutrophils Contribute to Lung Pathology during Murine Mycoplasma Infection

RAD Assignment Number

1405

Presenter Name

Maximillion T. Mize

Abstract

Background: Current research cannot fully explain how mycoplasma promote airway inflammation. It is no surprise that current vaccines promote lung damage. We showed that T-cells drive resistance and pathology in mice infected with Mycoplasma pulmonis. T-cells are important in vaccine-associated immunity. Our goal is to improve the effectiveness of current vaccines by understanding how T-cells contribute to disease outcome.

IL-17A is secreted by T-cells and activates neutrophils during infection. However, overzealous IL-17A production activates immune responses that cause disease. We found elevated IL-17A mRNA and protein levels in mice infected with M. pulmonis. Lung lesions in cattle infected with Mycoplasma mycoides contain IL-17A. What IL-17A does during disease is still not known. I hypothesis that IL-17A contributes to disease pathology during murine mycoplasma infection.

Methods: M. pulmonis is a natural pathogen of mice, infection mimics other mycoplasma diseases. Here, BALB/c mice were infected with M. pulmonis as previously described. Disease was monitored in mice receiving either PBS or antibodies against IL-17A and Ly6G. Flow cytometry and immunostaining were used to identify phagocytes and IL-17A+ lymphocytes in the lung.

Results: T-cells produce IL-17A during infection with M. pulmonis. IL-17A+ T-cells exist in the lungs prior to infection and may contribute to the rapid recruitment of neutrophils into the respiratory tract immediately after inoculation. αβ CD4+ T-cells was the predominant T-cell population producing IL-17A throughout infection.

By Day 14, αβ T-cells in the lungs and lower respiratory lymph nodes were able to secrete IL-17A alone, or in combination with IFN-γ. Expression of ROR-γt was not required for IL-17A production by αβ T-cells in the lung. Immunostaining revealed that IL-17A+ CD4+, and not IL-17A+ CD8+, were located within inflammatory lesions.

Neutralizing IL-17A reduced host damage without impacting bacterial burden. Neutrophilic lesions were lower in response to IL-17A neutralization. Depletion of neutrophils was more effective at reducing pathology when compared to IL-17A neutralization. Combining IL-17A neutralization with neutrophil depletion failed to further reduce the disease pathogenesis.

Conclusions: Neutrophils and IL-17A+ T-cells contribute to pathogenesis during murine mycoplasma infection. These cells may act independently to promote inflammation. IL-17A may exacerbate neutrophil-dependent pathology.

Research Area

Immunology

Presentation Type

Oral

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IL-17A(+) CD4(+) T-Cells and Neutrophils Contribute to Lung Pathology during Murine Mycoplasma Infection

Background: Current research cannot fully explain how mycoplasma promote airway inflammation. It is no surprise that current vaccines promote lung damage. We showed that T-cells drive resistance and pathology in mice infected with Mycoplasma pulmonis. T-cells are important in vaccine-associated immunity. Our goal is to improve the effectiveness of current vaccines by understanding how T-cells contribute to disease outcome.

IL-17A is secreted by T-cells and activates neutrophils during infection. However, overzealous IL-17A production activates immune responses that cause disease. We found elevated IL-17A mRNA and protein levels in mice infected with M. pulmonis. Lung lesions in cattle infected with Mycoplasma mycoides contain IL-17A. What IL-17A does during disease is still not known. I hypothesis that IL-17A contributes to disease pathology during murine mycoplasma infection.

Methods: M. pulmonis is a natural pathogen of mice, infection mimics other mycoplasma diseases. Here, BALB/c mice were infected with M. pulmonis as previously described. Disease was monitored in mice receiving either PBS or antibodies against IL-17A and Ly6G. Flow cytometry and immunostaining were used to identify phagocytes and IL-17A+ lymphocytes in the lung.

Results: T-cells produce IL-17A during infection with M. pulmonis. IL-17A+ T-cells exist in the lungs prior to infection and may contribute to the rapid recruitment of neutrophils into the respiratory tract immediately after inoculation. αβ CD4+ T-cells was the predominant T-cell population producing IL-17A throughout infection.

By Day 14, αβ T-cells in the lungs and lower respiratory lymph nodes were able to secrete IL-17A alone, or in combination with IFN-γ. Expression of ROR-γt was not required for IL-17A production by αβ T-cells in the lung. Immunostaining revealed that IL-17A+ CD4+, and not IL-17A+ CD8+, were located within inflammatory lesions.

Neutralizing IL-17A reduced host damage without impacting bacterial burden. Neutrophilic lesions were lower in response to IL-17A neutralization. Depletion of neutrophils was more effective at reducing pathology when compared to IL-17A neutralization. Combining IL-17A neutralization with neutrophil depletion failed to further reduce the disease pathogenesis.

Conclusions: Neutrophils and IL-17A+ T-cells contribute to pathogenesis during murine mycoplasma infection. These cells may act independently to promote inflammation. IL-17A may exacerbate neutrophil-dependent pathology.