Influenza A Virus Infection Induces Apical Redistribution of Na+, K+-ATPase in Lung Epithelial Cells In Vitro and In Vivo

ABSTRACT Bronchiolar epithelial cells are the prime targets for influenza A virus infection. It still remains to be clarified which signals are generated from these cells to initiate an immune response. Among chemokines, viral infection of primary lung epithelial cells triggered exclusively the release of CXCL8/interleukin-8 (IL-8), which contrasts with our previous observation that influenza A virus induced in monocytes the expression of mononuclear-leukocyte-attracting chemokines and even suppressed the production of neutrophil-attracting chemokines. Therefore, we speculated that it may be advantageous for respiratory epithelial cells to release primarily neutrophil-attracting CXCL8/IL-8 since neutrophils rapidly remove necrotic debris and are the first line of defense against bacterial superinfections. This concept has also been supported by our finding that influenza A virus infection led to necrosis of lung epithelial cells. This is in striking contrast to previous studies where influenza A virus infection induced apoptosis in monocytes and epithelial cells from origins other than the lung. Thus, the cell type instead of the virus determines which death pathway will be followed. In addition to the release of CXCL8/IL-8, we obtained a massive release of macrophage migration inhibitory factor (MIF) from virus-infected lung cells. However, whereas the CXCL8/IL-8 secretion was accompanied by induced gene activation, the transcription rate of MIF remained unchanged during the infection course and the virus-induced MIF release was predominantly a discharge from intracellular stores, suggesting that MIF is passively released upon cell death. Despite virus induced necrosis, the passively liberated MIF remained bioactive. Considering the well-established immunostimulatory effects of MIF on different leukocyte subsets, is its very likely that enhanced levels of MIF may contribute to the host immune response during the acute phase of influenza A virus infection in humans.

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Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo

Veterinary Research ◽

10.1186/s13567-019-0695-2 ◽

2019 ◽

Vol 50 (1) ◽

Author(s):

Guihong Yang ◽

Huipeng Huang ◽

Mengyao Tang ◽

Zifeng Cai ◽

Cuiqin Huang ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

A549 Cells ◽

Virus Challenge ◽

Neuromedin B ◽

Influenza A Virus Infection

Abstract The peptide neuromedin B (NMB) and its receptor (NMBR) represent a system (NMB/NMBR) of neuromodulation. Here, it was demonstrated that the expression of NMBR in cells or murine lung tissues was clearly upregulated in response to H1N1/PR8 influenza A virus infection. Furthermore, the in vitro and in vivo activities of NMB/NMBR during PR8 infection were investigated. It was observed that A549 cells lacking endogenous NMBR were more susceptible to virus infection than control cells, as evidenced by the increased virus production in the cells. Interestingly, a significant decrease in IFN-α and increased IL-6 expression were observed in these cells. The role of this system in innate immunity against PR8 infection was probed by treating mice with NMB. The NMB-treated mice were less susceptible to virus challenge, as evidenced by increased survival, increased body weight, and decreased viral NP expression compared with the control animals. Additionally, the results showed that exogenous NMB not only enhanced IFN-α expression but also appeared to inhibit the expression of NP and IL-6 in PR8-infected cells and animals. As expected, opposing effects were observed in the NMBR antagonist-treated cells and mice, which further confirmed the effects of NMB. Together, these data suggest that NMB/NMBR may be an important component of the host defence against influenza A virus infection. Thus, these proteins may serve as promising candidates for the development of novel antiviral drugs.

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