In Susceptible Mice Infected with M. pulmonis, Host Lung Damage is Associated with Recruitment of IL-17A+ Lymphocytes and Neutrophils into the Lung

Background: Possessing the smallest genomes, mycoplasma induce debilitating pneumonia in humans and animals resulting in chronic airway inflammation. Exacerbating previously acquired respiratory conditions (i.e. asthma), mycoplasma have evolved to resist antibiotics1-3. Current vaccines induce the same damage seen during actual infection. A proinflammatory cytokine contributing to chronic pathology and neutrophil-mediated host protection, IL-17A is secreted during infection with mycoplasma. Here, we investigate whether IL-17A can promote damage characteristic of mycoplasma disease. Our results will help development of vaccines that confer protection and lack side-effects. Methods: Murine pneumonia, induced by M. pulmonis, resembles the pulmonary pathogenesis seen in human mycoplasma diseases. Furthermore, BALB/c models have been well established for studying chronic respiratory mycoplasma infection4-6. Briefly, M. pulmonis was administered intra-nasally. At select time points post infection, mice were sacrificed and aspects of pulmonary pathogenesis analyzed. Results: Injecting neutralizing antibodies against IL-17A into BALB/c mice reduced inflammation during infection without influencing bacterial burden. Attenuating the effects of IL-17A reduced both airway cell numbers and total lung IL-17A+ lymphocytes by Day (14). The increase in IL-17A+ cells was associated with increased airway neutrophils, appearing as early as Day (1) post-infection with M. pulmonis. The presence of neutrophils appears alongside CD4+, CD8+, and γδ T-cells that secrete IL-17A early during infection. By Day (9) post-infection, the described T-cell populations are replaced by CD4+, SCA-1+, and NK cells that contribute to IL-17A levels. Although IL-17A production by CD4+ T-cells reaches its maximum response at Day (1) post-infection, this was the only T-cell population that persisted in their production of IL-17A by Day (14). Interesting, neutralizing the effect of IL-17A during early disease results in more severe inflammation when compared to both controls and animals starting treatment five days’ post-infection. The generation of IL-17A+ lymphocytes, and subsequent recruitment of neutrophils was associated with disease pathogenesis. Conclusions: During infection with M. pulmonis, neutrophil recruitment into the lungs is associated with the presence of IL-17A+ lymphocytes. Neutrophils and IL-17A+ cells drive host damage; neutralizing IL-17A reduces airway neutrophils, total IL-17A+ lung cells and host damage. Blocking IL-17A lowers lung lesion development, thus IL-17A and neutrophils promote respiratory damage. Surprisingly, blocking IL-17A during the innate response results in more severe inflammation when compared to neutralizing IL-17A once adaptive immunity takes over. Thus, IL-17A may have protective effects during the early phases of mycoplasma disease.