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Infect Immun. 2018 Aug 22;86(9). pii: e00292-18. doi: 10.1128/IAI.00292-18. Print 2018 Sep.

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

Author information

1
Department of Pharmaceutical Sciences and UNT Preclinical Services, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, USA.
2
Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, Texas, USA.
3
Department of Pharmaceutical Sciences and UNT Preclinical Services, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, USA Jerry.Simecka@unthsc.edu.

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 Mycoplasma pulmonis Neutralizing the function of IL-17A using anti-IL-17A antibodies reduced disease severity during M. pulmonis 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 M. pulmonis 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.

KEYWORDS:

IL-17; Th17 cells; bacterial; cytokines; inflammation; lung infection; mucosa; mycoplasma

PMID:
29986888
PMCID:
PMC6105906
DOI:
10.1128/IAI.00292-18
[Indexed for MEDLINE]
Free PMC Article

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