Cell-Mediated Immune Response During Experimental Acute Infection with Bovine Viral Diarrhoea Virus: Evaluation of Blood Parameters

Abstract

Acute infections with bovine viral diarrhoea virus (BVDV), a major pathogen of cattle, are often asymptomatic or produce only mild clinical symptoms. However, they may play an important role in the bovine respiratory disease complex by exerting a marked immunosuppressive effect, as a result of the death of the immunocompetent cell populations involved in controlling innate and adaptive immune responses, together with a marked reduction of both cytokine expression and co-stimulatory molecule synthesis. Although experimental research and field studies have shown that acute BVDV infection enhances susceptibility to secondary infection, the precise mechanism involved in BVDV-induced immunosuppression remains unclear. The present study is aimed at measuring a range of blood parameters in a single group of fourteen calves infected with non-cytopathic BVDV-1. Focus has been put on those related to the cell-mediated immune response just as leucocyte populations and lymphocyte subpopulations, serum concentrations of cytokines (IL-1b, TNF-a, IFN-c, IL-12, IL-4 and IL-10) and acute phase proteins [haptoglobin, serum amyloid A (SAA), fibrinogen and albumin], as well as BVDV-specific antibodies and viremia. After non-cytopathic BVDV-1 infection, clinical signs intensity was never more than moderate coinciding with the presence of viremia and leucocyte and lymphocyte depletion. An early increase in TNF-a, IFN-c and IL-12 levels in contrast to IL-1b was observed in line with a raise in haptoglobin and SAA levels on the latest days of the study. As regards IL-4 levels, no evidence was found of any changes. However, a slight increase in IL-10 was observed, matching up the TNF-a decline during the acute phase response. These findings would help to increase our knowledge of the immune mechanisms involved in acute infection with non-cytopathic BVDV-1 strains, suggesting the existence of a clear tendency towards a type 1 immune response, thereby enhancing resistance against viral infections.

Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves

“…As infection-induced changes in circulating concentrations of these specific cytokines can occur earlier than 4 d postinoculation (reviewed by Kelling and Topliff, 2013), changes may have been missed due to the sampling schedule followed in the current study. Results from a recent study (Molina et al, 2012) demonstrated earlier increases in serum TNF-α, IFN-γ, and IL-12 and an associated decrease in IL-1β in older calves (8 to 9 . Treatment means that differed on a specific day are indicated by *P < 0.10 (strong trend), **P < 0.05, ***P < 0.01, and ****P < 0.001.…”

Type I and III IFNs Produced by Plasmacytoid Dendritic Cells in Response to a Member of theFlaviviridaeSuppress Cellular Immune Responses

“…The disease state induced can range from acute, subclinical infections of immunocompetent cattle to persistent infection that can lead to mucosal disease, which is usually fatal due to superinfection of persistently infected animals with antigenically homologous cp virus or de novo generation of a cp variant of the persisting ncp virus (3). BVDV has been shown to infect cells pivotal in control of both the innate and adaptive immune responses (4), and infection has been shown to be immunosuppressive (5,6). Transient immunosuppression occurs in acutely infected animals (7), permitting colonization and replication by opportunistic pathogens (8,9).…”

Immunopathologic Changes in the Thymus of Calves Pre-infected with BVDV and Challenged with BHV-1

“…A previous study by our group focused on the first 12 dpi with BVDV revealed a transitory decrease in monocytes (Molina et al., ). After these 12 days of infection with BVDV, circulating monocytes were restored to normal values and maintained with no significant changes after BHV‐1 inoculation (Molina et al., ), coinciding with systemic results from other authors (Falkenberg et al., ).…”

“…Hence, to maintain a stable population, there must be an influx of new T cells replacing those that are decaying (Stromberg and Antia, ). In this study, we observed an increase in CD8+ T cells in the thymus medulla of BVDV‐infected calves that might take place as a result of a compensatory mechanism of cytotoxic T lymphocyte (CTL) mobilization in response to the intense CD8 systemic depletion observed in the coinfected animals during the acute phase of BVD (Molina et al., ), which was maintained after BHV‐1 inoculation (Molina et al., ).…”

“…In this experiment, a progressive decrease in the number of WC1+ δγ T cells was observed in the medulla in both groups of animals, with significantly higher values in the coinfected group only at 4 and 7 dpi. At the systemic level, these animals did not show remarkable differences between groups, except for a peak in pre‐infected calves at 12 dpi with BVDV (0 dpi with BHV‐1) (Molina et al., , ). These results, in agreement with previous works, do not clearly suggest a major role of δγ T cells in resisting BVDV infection (Howard et al., ).…”