Differential pulmonary immunopathology of domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) with Mycoplasma ovipneumoniae infection: a retrospective study

Authors: GROSSMAN, PAIGE - Washington State University; Schneider, David; Herndon, David; KNOWLES, DONALD - Washington State University; Highland, Margaret

Submitted to: Comparative Immunology Microbiology and Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2021
Publication Date: 3/3/2021
Citation: Grossman, P.C., Schneider, D.A., Herndon, D.R., Knowles, D.P., Highland, M.A. 2021. Differential pulmonary immunopathology of domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) with Mycoplasma ovipneumoniae infection: a retrospective study. Comparative Immunology Microbiology and Infectious Diseases. 76. Article 101641. https://doi.org/10.1016/j.cimid.2021.101641.
DOI: https://doi.org/10.1016/j.cimid.2021.101641

Interpretive Summary: Mycoplasma ovipneumoniae is a respiratory pathogen that impacts domestic sheep (DS) and bighorn sheep (BHS), and is considered by some to be the primary agent of BHS pneumonia. While experimental and observational field data indicate BHS are more susceptible than DS to bacterial pneumonia, the immune response to M. ovipneumoniae infection remains unexamined, and may provide insight into why bighorn sheep are seemingly more susceptible to M. ovipneumoniae-associated pneumonia. Perhaps more importantly, determining the type of immune response that DS mount to M. ovipneumoniae infection, given the current information that DS are more resilient to infection, may guide development of protective vaccines for use in both species. This would be possible due to the use of vaccine adjuvants that would stimulate the desired/appropriate immune response.

Technical Abstract: Mycoplasma ovipneumoniae is a respiratory pathogen that impacts domestic sheep (Ovis aries; DS) and bighorn sheep (Ovis canadensis; BHS). While experimental and observational field data indicate BHS are more susceptible than DS to bacterial pneumonia, immunopathologic correlates of this susceptibility difference in relation to M. ovipneumoniae infection remain uncharacterized. Typical histopathologic findings in lungs of both species infected with M. ovipneumoniae included hyperplasia of bronchiolar epithelium and bronchial associated lymphoid tissue (BALT), and mononuclear leukocyte infiltration around bronchioles and in adjacent alveolar walls. While similar by light microscopic evaluation, we hypothesized that a differential interspecies immunopathologic pulmonary response to M. ovipneumoniae infection occurs in DS and BHS. To characterize this response, a retrospective study utilizing formalin-fixed, paraffin-embedded (FFPE) lung tissues from 8 uninfected and 8 infected sheep of each species was performed. FFPE tissue was H&E stained for light microscopic evaluation and immunohistochemically stained with antibodies specific for cytokine and leukocyte markers. Of 33 antibodies tested, 6 exhibited immunoreactivity in both species: T cell marker CD3, B cell markers CD20 and CD79a, macrophage markers CD163 and Iba1, and cytokine IL-17. Immunohistochemistry (IHC) stained tissue slides were scanned for colorimetric digital analysis. Species and infection status factors were evaluated by two-way ANOVA, and Tukey’s multiple comparison tests were performed (P<0.05 significant). CD3 and CD163 were more abundant in infected BHS as compared to both uninfected BHS and infected DS. CD20 was more abundant in infected DS as compared to both uninfected DS and infected BHS. CD79a was more abundant in infected DS as compared to uninfected DS. IL-17 abundance was less in infected DS as compared to uninfected DS. No significant differences were observed with Iba-1 abundance. These findings suggest DS and BHS have a differential immune response to M. ovipneumoniae infection which may in part explain the documented susceptibility difference.