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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 and Secula, Aurelie and Rancon, Camille and Boulesteix, Olivier and Pinard, Anne and Deslis, Alain and Hägglund, Sara and Salem, Elias and Cassard, Herve and Näslund, Katarina and Gaudino, Maria and Moreno, Ana and Brocchi, Emiliana and Delverdier, Maxence and Zohari, Siamak and Baranowski, Eric and Valarcher, Jean-Francois and Ducatez, Mariette F. and Meyer, Gilles (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. Microbiology Spectrum. 9 :3 , e01690-21
[Research article]

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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.

Authors/Creators:Lion, Adrien and Secula, Aurelie and Rancon, Camille and Boulesteix, Olivier and Pinard, Anne and Deslis, Alain and Hägglund, Sara and Salem, Elias and Cassard, Herve and Näslund, Katarina and Gaudino, Maria and Moreno, Ana and Brocchi, Emiliana and Delverdier, Maxence and Zohari, Siamak and Baranowski, Eric and Valarcher, Jean-Francois and Ducatez, Mariette F. and Meyer, Gilles
Title: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
Series Name/Journal:Microbiology Spectrum
Year of publishing :2021
Volume:9
Number:3
Article number:e01690-21
Number of Pages:20
Publisher:AMER SOC MICROBIOLOGY
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:influenza D virus, Mycoplasma bovis, cattle, bovine respiratory disease, coinfection, immune response
URN:NBN:urn:nbn:se:slu:epsilon-p-115798
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-115798
Additional ID:
Type of IDID
DOI10.1128/Spectrum.01690-21
Web of Science (WoS)000736124700179
ID Code:26849
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:28 Jan 2022 10:25
Metadata Last Modified:17 May 2022 07:22

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