Proteomic and Lipidomic Profiling of Calves Experimentally Co-Infected with Influenza D Virus and <i>Mycoplasma bovis</i>: Insights into the Host–Pathogen Interactions
Ignacio Alvarez,
Mariette Ducatez,
Yongzhi Guo,
Adrien Lion,
Anna Widgren,
Marc Dubourdeau,
Vincent Baillif,
Laure Saias,
Siamak Zohari,
Jonas Bergquist,
Gilles Meyer,
Jean-Francois Valarcher,
Sara Hägglund
Affiliations
Ignacio Alvarez
Division of Ruminant Medicine, Department of Clinical Sciences, Swedish University of Agriculture Sciences, 8 Almas Allé, 75007 Uppsala, Sweden
Mariette Ducatez
IHAP, Université de Tolouse, INRAE, ENVT, 31076 Toulouse, France
Yongzhi Guo
Division of Ruminant Medicine, Department of Clinical Sciences, Swedish University of Agriculture Sciences, 8 Almas Allé, 75007 Uppsala, Sweden
Adrien Lion
IHAP, Université de Tolouse, INRAE, ENVT, 31076 Toulouse, France
Anna Widgren
Department of Chemistry-BMC, Analytical Chemistry and Neurochemistry, Uppsala University, Husargatan 3, 75124 Uppsala, Sweden
Marc Dubourdeau
Ambiotis SAS, 3 Rue des Satellites, 31400 Toulouse, France
Vincent Baillif
Ambiotis SAS, 3 Rue des Satellites, 31400 Toulouse, France
Laure Saias
Ambiotis SAS, 3 Rue des Satellites, 31400 Toulouse, France
Siamak Zohari
Department of Microbiology, Swedish Veterinary Agency, Ullsvägen 2B, 75189 Uppsala, Sweden
Jonas Bergquist
Department of Chemistry-BMC, Analytical Chemistry and Neurochemistry, Uppsala University, Husargatan 3, 75124 Uppsala, Sweden
Gilles Meyer
IHAP, Université de Tolouse, INRAE, ENVT, 31076 Toulouse, France
Jean-Francois Valarcher
Division of Ruminant Medicine, Department of Clinical Sciences, Swedish University of Agriculture Sciences, 8 Almas Allé, 75007 Uppsala, Sweden
Sara Hägglund
Division of Ruminant Medicine, Department of Clinical Sciences, Swedish University of Agriculture Sciences, 8 Almas Allé, 75007 Uppsala, Sweden
The role of Influenza D virus (IDV) in bovine respiratory disease remains unclear. An in vivo experiment resulted in increased clinical signs, lesions, and pathogen replication in calves co-infected with IDV and Mycoplasma bovis (M. bovis), compared to single-infected calves. The present study aimed to elucidate the host–pathogen interactions and profile the kinetics of lipid mediators in the airways of these calves. Bronchoalveolar lavage (BAL) samples collected at 2 days post-infection (dpi) were used for proteomic analyses by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, lipidomic analyses were performed by LC-MS/MS on BAL samples collected at 2, 7 and 14 dpi. Whereas M. bovis induced the expression of proteins involved in fibrin formation, IDV co-infection counteracted this coagulation mechanism and downregulated other acute-phase response proteins, such as complement component 4 (C4) and plasminogen (PLG). The reduced inflammatory response against M. bovis likely resulted in increased M. bovis replication and delayed M. bovis clearance, which led to a significantly increased abundance of oxylipids in co-infected calves. The identified induced oxylipids mainly derived from arachidonic acid; were likely oxidized by COX-1, COX-2, and LOX-5; and peaked at 7 dpi. This paper presents the first characterization of BAL proteome and lipid mediator kinetics in response to IDV and M. bovis infection in cattle and raises hypotheses regarding how IDV acts as a co-pathogen in bovine respiratory disease.