RETRACTED: Contribution of Host Immune Responses against Influenza D Virus Infection toward Secondary Bacterial Infection in a Mouse Model

Abstract

Influenza D viruses (IDV) are known to co-circulate with viral and bacterial pathogens in cattle and other ruminants. Currently, there is limited knowledge regarding host responses to IDV infection and whether IDV infection affects host susceptibility to secondary bacterial infections. To begin to address this gap in knowledge, the current study utilized a combination of in vivo and in vitro approaches to evaluate host cellular responses against primary IDV infection and secondary bacterial infection with Staphylococcus aureus (S. aureus). Primary IDV infection in mice did not result in clinical signs of disease and it did not enhance the susceptibility to secondary S. aureus infection. Rather, IDV infection appeared to protect mice from the usual clinical features of secondary bacterial infection, as demonstrated by improved weight loss, survival, and recovery when compared to S. aureus infection alone. We found a notable increase in IFN-β expression following IDV infection while utilizing human alveolar epithelial A549 cells to analyze early anti-viral responses to IDV infection. These results demonstrate for the first time that IDV infection does not increase the susceptibility to secondary bacterial infection with S. aureus, with evidence that anti-viral immune responses during IDV infection might protect the host against these potentially deadly outcomes.

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

“…Conversely, IAV infection was also shown to induce alveolar macrophage depletion, increasing the susceptibility to secondary infection ( 21 , 34 , 35 ). In agreement with our cattle study, Skelton et al ( 36 ) recently showed that intratracheal IDV infection in mice increased the recruitment of neutrophils and lymphocytes and did not deplete macrophage counts in the lungs of mice euthanized at 7 dpi. On the other hand, no clinical signs were observed in another study after IDV infection alone in mice ( 28 ).…”

“…As we performed coinfections and not superinfections, comparisons with previous publications of IDV superinfections in calves or mice are difficult. Using IDV, Skelton et al showed that intratracheal IDV inoculation in mice protected against a secondary Staphylococcus aureus infection ( 36 ), suggesting that macrophages may be involved in mediating protection from secondary bacterial challenge by neutrophils and lymphocytes. In addition to differences in infection kinetics, the types of bacteria used in each challenge may also explain the exacerbation of the respiratory disease we observed for IDV coinfection with M. bovis in calves.…”

The first decade of research advances in influenza D virus

“…The results showed that primary IDV infection in cattle did not enhance the disease caused by the secondary MHA infection [79]. Interestingly, this result was similar to that of an independent mice study, which found that IDV infection in mice did not increase the susceptibility to secondary Staphylococcus aureus infection, but was protective against clinical signs of the secondary bacterial infection [81]. More studies are needed to define synergistic or antagonistic actions behind the opportunistic infection with IDV and determine the underlying mechanisms of IDV pathogenicity in IDV-associated coinfection.…”

“…Ferrets have been used as a surrogate for influenza virus infection of humans. No clinical signs of disease were reported in these animals infected with IDVs [4, 81–83]. In ferrets, IDV replicated in the nasal turbinate but not in the lower respiratory tract [4].…”

LsrR, the effector of AI-2 quorum sensing, is vital for the H2O2 stress response in mammary pathogenic Escherichia coli

“…Previous studies showed that bacteria express a series of stress proteins to protect themselves from environmental stimuli and to resist adverse environmental pressures such as antibiotics, oxidative stress, acid–base, and osmotic pressure [ 6 – 10 ]. It is generally understood that bacterial infection can trigger innate immune response [ 11 , 12 ]. Once the pathogenic bacteria infect the host, they are phagocytosed by the host immune cells and macrophages and heterophile cells may produce oxidative bursts in response to pathogens [ 13 , 14 ].…”