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Research article - Peer-reviewed, 2021

Enhanced Pathogenesis Caused by Influenza D Virus and Mycoplasma bovis Coinfection in Calves: a Disease Severity Linked with Overexpression of IFN-gamma as a Key Player of the Enhanced Innate Immune Response in Lungs

Lion, Adrien; Secula, Aurelie; Rancon, Camille; Boulesteix, Olivier; Pinard, Anne; Deslis, Alain; Hagglund, Sara; Salem, Elias; Cassard, Herve; Naslund, Katarina; Gaudino, Maria; Moreno, Ana; Brocchi, Emiliana; Delverdier, Maxence; Zohari, Siamak; Baranowski, Eric; Valarcher, Jean-Francois; Ducatez, Mariette F.; Meyer, Gilles;

Abstract

Bovine respiratory disease (BRD) is a major disease of young cattle whose etiology lies in complex interactions between pathogens and environmental and host factors. Despite a high frequency of codetection of respiratory pathogens in BRD, data on the molecular mechanisms and pathogenesis associated with viral and bacterial interactions are still limited. In this study, we investigated the effects of a coinfection with influenza D virus (IDV) and Mycoplasma bovis in cattle. Naive calves were infected by aerosol with a French IDV strain and an M. bovis strain. The combined infection shortened the incubation period, worsened the disease, and led to more severe macroscopic and microscopic lesions compared to these parameters in calves infected with only one pathogen. In addition, IDV promoted colonization of the lower respiratory tract (LRT) by M. bovis and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The gamma interferon (IFN-gamma) gene was shown to be the gene most statistically overexpressed after coinfection at 2 days postinfection (dpi) and at least until 7 dpi, which correlated with the high level of lymphocytes in the LRT. Downregulation of the PACE4 and TMPRSS2 endoprotease genes was also highlighted, being a possible reason for the faster clearance of IDV in the lungs of coinfected animals. Taken together, our coinfection model with two respiratory pathogens that when present alone induce moderate clinical signs of disease was shown to increase the severity of the disease in young cattle and a strong transcriptomic innate immune response in the LRT, especially for IFN-gamma.IMPORTANCE Bovine respiratory disease (BRD) is among the most prevalent diseases in young cattle. BRD is due to complex interactions between viruses and/or bacteria, most of which have a moderate individual pathogenicity. In this study, we showed that coinfection with influenza D virus (IDV) and Mycoplasma bovis increased the severity of the respiratory disease in calves in comparison with IDV or M. bovis infection. IDV promoted M. bovis colonization of the lower respiratory tract and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The IFN-gamma gene in particular was highly overexpressed after coinfection, correlated with the disease severity, immune response, and white cell recruitment in the lungs. In conclusion, we showed that IDV facilitates coinfections within the BRD complex by modulating the local innate immune response, providing new insights into the mechanisms involved in severe respiratory diseases.

Keywords

influenza D virus; Mycoplasma bovis; cattle; bovine respiratory disease; coinfection; immune response

Published in

Microbiology Spectrum

2021, volume: 9, number: 3, article number: e01690-21
Publisher: AMER SOC MICROBIOLOGY

Authors' information

Lion, Adrien
Universite de Toulouse
Secula, Aurelie
INRAE
Rancon, Camille
Universite de Toulouse
Boulesteix, Olivier
INRAE
Pinard, Anne
INRAE
Deslis, Alain
INRAE
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Salem, Elias
Universite de Toulouse
Cassard, Herve
Universite de Toulouse
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Gaudino, Maria
Universite de Toulouse
Moreno, Ana
IZS Lombardia e Emilia
Brocchi, Emiliana
IZS Lombardia e Emilia
Delverdier, Maxence
Universite de Toulouse
Zohari, Siamak
National Veterinary Institute SVA
Baranowski, Eric
Universite de Toulouse
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Ducatez, Mariette F.
Universite de Toulouse
Meyer, Gilles
Universite de Toulouse

UKÄ Subject classification

Clinical Science

Publication Identifiers

DOI: https://doi.org/10.1128/Spectrum.01690-21

URI (permanent link to this page)

https://res.slu.se/id/publ/115798