Interleukin-17A Exacerbates Disease Severity in BALB/c Mice Susceptible to Lung Infection with Mycoplasma pulmonis

Abstract

Mycoplasmas are atypical bacteria that disrupt the immune response to promote respiratory tract infections and secondary complications. However, not every immunologic response that protects or damages the host during mycoplasma infection is known. Interleukin-17A (IL-17A) is elevated in individuals infected with mycoplasmas, but how IL-17A and its cellular sources dictate disease outcome remains unclear. Here, IL-17A is hypothesized to worsen disease in individuals susceptible to mycoplasma infection. Thus, monoclonal anti-IL-17A antibodies were given to disease-susceptible BALB/c mice and disease-resistant C57BL/6 mice infected with Neutralizing the function of IL-17A using anti-IL-17A antibodies reduced disease severity during infection in BALB/c, but not C57BL/6, mice. Neutralizing IL-17A also reduced the incidence of neutrophilic lung lesions during infection in BALB/c mice. Reduced pathology occurred without impacting the bacterial burden, demonstrating that IL-17A is not required for mycoplasma clearance. The main source of IL-17A throughout infection in BALB/c mice was CD4 T cells, and neutralizing IL-17A after infiltration of the lungs by T cells reduced disease severity, identifying the Th17 response as a herald of late mycoplasma pathology in susceptible mice. Neutralizing IL-17A did not further reduce disease during infection in BALB/c mice depleted of neutrophils, suggesting that IL-17A requires the presence of pulmonary neutrophils to worsen respiratory pathology. IL-17A is a pathological element of murine respiratory mycoplasma infection. Using monoclonal antibodies to neutralize IL-17A could reduce disease severity during mycoplasma infection in humans and domesticated animals.

Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice

“…The elevation of IL-17A levels during mycoplasma infection in D2 mice, but not B6 mice, is associated with disease pathology, including the recruitment of pulmonary neutrophils (Fig. 6B), which has been also reported in other studies (31). These results suggest that the function of IL-17A in the immune response to mycoplasma may be different based on the genetic background.…”

A Dynamic Variation of Pulmonary ACE2 Is Required to Modulate Neutrophilic Inflammation in Response to Pseudomonas aeruginosa Lung Infection in Mice

“…It has been reported that IL-17 is critical in mediating pulmonary neutrophil infiltration, whereas the lungs encountered infectious insults (40)(41)(42)(43)(44). Our previous studies in necrotizing enterocolitisinduced lung injury also indicated that IL-17 is critical in neutrophilic lung inflammation (45).…”

Calves Infected with Virulent and Attenuated Mycoplasma bovis Strains Have Upregulated Th17 Inflammatory and Th1 Protective Responses, Respectively

“…Some studies have reported that IL-17 is essential for defense against Mycoplasma pulmonis [10], Mycoplasma pneumoniae [11], and a secondary Listeria infection [10]. However, others demonstrated that M. pulmonis induced Th17 response associated with pathogenesis, as shown by the observation that neutralization of IL-17A with anti-IL-17A antibodies reduced disease severity and the incidence of neutrophilic lung lesions during M. pulmonis infection in mice [12]. Recently, virulent M. bovis has been reported to induce IL-17 production in the peripheral blood mononuclear cells (PBMCs) of calves [13], whereas the recombinant bovine IL-17A could not enhance the capacity of neutrophils to destroy M. bovis in vitro [8].…”