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

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

La diversité des agents pathogènes respiratoires bovins : faut-il de nouvelles valences vaccinales ?

Depuis quelques années, de nouvelles méthodes très performantes de détection des virus et bactéries ont permis d’identifier de nouveaux agents pathogènes potentiellement impliqués dans les bronchopneumonies infectieuses des jeunes bovins. Elles ont aussi confirmé l’importance des co-infections et la complexité des situations sur le terrain, suscitant de nombreuses questions sur les moyens de gestion, notamment la prévention vaccinale. Cet article fait le point sur les connaissances actuelles des agents pathogènes respiratoires mineurs, leurs associations et les conséquences sur la vaccination.Les bronchopneumonies infectieuses (BPI) des jeunes bovins sont des affections multifactorielles fréquentes dont la gravité dépend des animaux, des conditions d’élevage et des agents pathogènes respiratoires présents. La diversité des agents pathogènes connus, la découverte de nouveaux virus potentiellement impliqués et les co-infections fréquentes en élevage compliquent la gestion des BPI, notamment leur prévention vaccinale

Vitamin D deficiency during late pregnancy mediates placenta-associated complications

International audienceAbstract During pregnancy, maternal vitamin D insufficiency could increase the risk of preeclampsia. Aim of the study was to evaluate the relationship between vitamin D status and the occurrence of placenta-mediated complications (PMCs) in a population at high risk. A prospective multicenter cohort study of 200 pregnant patients was conducted. The vitamin D level of patients with placenta-mediated complications was lower at 32 weeks compared to uncomplicated pregnancies ( P = 0.001). At 32 weeks, the risk of occurrence of PMCs was five times higher in patients with vitamin D deficiency (RR: 5.14 95% CI (1.50–17.55)) compared to patients with normal vitamin D levels. There was a strong, inverse relationship between serum 25(OH)D levels at 32 weeks and the subsequent risk of PMCs ( P = 0.001). At 32 weeks, the vitamin D level of patients with late-onset PMCs was lower than the one of patients with early-onset PMCs and of patients without PMCs ( P < 0.0001). These results suggest a role of vitamin D in the maintenance of placental performance and therefore in the prevention of the onset of late PMC