IL-17A ENHANCES DISEASE PATHOLOGY IN BALB/C MICE WHILE CONTRIBUTING TO HOST PROTECTION IN THE C57BL/6 STRAIN DURING INFECTION WITH MYCOPLASMA PULMONIS

Mycoplasma are bacterial organisms that can cause disease within the airways. Specifically, Mycoplasma pneumoniae causes pneumonia in humans which accounts for 30% of all cases of pneumonia worldwide with 100,000 cases per year resulting in hospitalization. This disease is characterized by a persistent infection, often leading to the initiation of chronic inflammation thus damaging the lungs and respiratory tract. In addition, it can also potentiate the disease severity of other respiratory conditions, such as asthma. Infection is often associated with close-quarter communities (i.e. dormitories, military barracks, etc.) allowing for quick spread of the disease. Furthermore, mycoplasma have also been found in livestock demonstrating that this bacteria has infiltrated important aspects of human society. Due to its resistance to antibiotics, such as penicillin, research has been forced to focus on alternative methods to treating disease. Interleukin-17A (IL-17A), a molecule secreted by immune cells, promotes inflammation and has also been implicated in the development of chronic inflammatory conditions. However, the role that IL-17A plays in chronic airway inflammation associated with Mycoplasma infection is currently unknown. Here, we use a mouse model of human pneumonia to determine if IL-17A contributes to tissue damage associated with disease. We demonstrate that targeting IL-17A with antibodies that block its biological function decreases disease severity within a susceptible BALB/c mouse strain. This alleviation was associated with decreased weight loss and lung damage when compared to identical mice not given antibody treatment. However, this method did not decrease bacterial numbers indicating that IL-17A is only associated with inflammation and not clearance of the organism. Interestingly, the opposite affect was seen in the more resistant C57BL/6 mouse strain leading our lab to believe that a genetic predisposition may be the underlying cause of IL-17A associated airway inflammation. A particular genetic background may dictate the amount of IL-17A released during infection, with high amounts predisposing an individual to severe and irreversible tissue damage, thus initiating a state of chronic inflammation. Purpose (a): Mycoplasma cause 30% of all cases of pneumonia worldwide. Infections induce chronic airway inflammation and has also been associated with the exacerbation of other respiratory diseases, like asthma. Due to a prevalence tied to close-quarter communities (dorms, military barracks, etc.), and the possession of a reservoir in livestock, it has infiltrated human society. Furthermore, the lack of a cell wall prevents this organism from being treated with beta-lactam antibiotics forcing research to focus on alternative treatment methods. While Interleukin-17A (IL-17A) has been linked to the induction of chronic inflammatory diseases, its role in mycoplasmosis is currently unknown. Here, we hypothesize that IL-17A leads to chronic inflammation, exacerbating disease pathogenesis. Methods (b): Female BALB/c and C57BL/6 mice, aged 6-12 weeks, were obtained from HARLAN Laboratory, Inc. Mice were housed in sterile microisolator cages supplied with sterile bedding, food, and water all given ad libitum. The UAB CT strain of M. pulmonis was administered intra-nasally to induce infection. Murine anti-IL-17A (αIL-17A) neutralizing antibody was administered intraperitoneal at a concentration 0.150 mg/mL daily. Results were analyzed via one-way and two-way ANOVA. Results (c): After administration of αIL-17A, BALB/c mice infected with M. pulmonis lost less weight when compared to identical mice given Phosphate Buffered Saline (PBS). In addition, infected mice given antibody displayed a reduction in gross lung lesions, however, bacterial burden was not affected. In contrast, infected C57BL/6 mice given αIL-17A antibodies demonstrated increased disease susceptibility associated with an increase in bacterial burden and gross lung lesions when compared to controls given PBS. Conclusions (d): While the presence of αIL-17A in infected BALB/c mice appears to exacerbate disease, this cytokine may play a protective role in C57BL/6 mice infected with the same pathogen. Lung damage decreased, independent of bacterial burden, in infected BALB/c mice administered antibody. This demonstrates that IL-17A does not play a role in pathogen clearance, but does potentiate chronic inflammation. In contrast, infected C57BL/6 mice given antibody had a slight increase in both lung damage and bacterial numbers indicating that IL-17A is needed to decrease disease pathogenesis. Thus, genotypic differences may play a role in how IL-17A influences an immune response through favoring the development of chronic diseases during bacterial infection.