tetano
Editor, Senior Moderator
Front Immunol. 2018 Oct 4;9:2297. doi: 10.3389/fimmu.2018.02297. eCollection 2018.
[h=1]Aflatoxin B[SUB]1[/SUB] Promotes Influenza Replication and Increases Virus Related Lung Damage via Activation of TLR4 Signaling.[/h] Sun Y[SUP]1,[/SUP][SUP]2[/SUP], Su J[SUP]1,[/SUP][SUP]2[/SUP], Liu Z[SUP]1,[/SUP][SUP]2[/SUP], Liu D[SUP]1,[/SUP][SUP]2[/SUP], Gan F[SUP]1,[/SUP][SUP]2[/SUP], Chen X[SUP]1,[/SUP][SUP]2[/SUP], Huang K[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Aflatoxin B[SUB]1[/SUB] (AFB[SUB]1[/SUB]), which alters immune responses to mammals, is one of the most common mycotoxins in feeds and food. Swine influenza virus (SIV) is a major pathogen of both animals and humans. However, there have been few studies about the relationship between AFB[SUB]1[/SUB] exposure and SIV replication. Here, for the first time, we investigated the involvement of AFB[SUB]1[/SUB] in SIV replication in vitro and in vivo and explored the underlying mechanism using multiple cell lines and mouse models. In vitro studies demonstrated that low concentrations of AFB[SUB]1[/SUB] (0.01-0.25 μg/ml) markedly promoted SIV replication as revealed by increased viral titers and matrix protein (M) mRNA and nucleoprotein (NP) levels in MDCK cells, A549 cells and PAMs. In vivo studies showed that 10-40 μg/kg of AFB[SUB]1[/SUB] exacerbated SIV infection in mice as illustrated by significantly higher lung virus titers, viral M mRNA levels, NP levels, lung indexes and more severe lung damage. Further study showed that AFB[SUB]1[/SUB] upregulated TLR4, but not other TLRs, in SIV-infected PAMs. Moreover, AFB[SUB]1[/SUB] activated TLR4 signaling as demonstrated by the increases of phosphorylated NFκB p65 and TNF-α release in PAMs and mice. In contrast, TLR4 knockdown or the use of BAY 11-7082, a specific inhibitor of NFκB, blocked the AFB[SUB]1[/SUB]-promoted SIV replication and inflammatory responses in PAMs. Furthermore, a TLR4-specific antagonist, TAK242, and TLR4 knockout both attenuated the AFB[SUB]1[/SUB]-promoted SIV replication, inflammation and lung damage in mice. We therefore conclude that AFB[SUB]1[/SUB] exposure aggravates SIV replication, inflammation and lung damage by activating TLR4-NFκB signaling.
[h=4]KEYWORDS:[/h] NFκB; TLR4; TNF-α; aflatoxin B1; inflammation; lung damage; replication; swine influenza virus
PMID: 30337931 PMCID: PMC6180208 DOI: 10.3389/fimmu.2018.02297
[h=1]Aflatoxin B[SUB]1[/SUB] Promotes Influenza Replication and Increases Virus Related Lung Damage via Activation of TLR4 Signaling.[/h] Sun Y[SUP]1,[/SUP][SUP]2[/SUP], Su J[SUP]1,[/SUP][SUP]2[/SUP], Liu Z[SUP]1,[/SUP][SUP]2[/SUP], Liu D[SUP]1,[/SUP][SUP]2[/SUP], Gan F[SUP]1,[/SUP][SUP]2[/SUP], Chen X[SUP]1,[/SUP][SUP]2[/SUP], Huang K[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Aflatoxin B[SUB]1[/SUB] (AFB[SUB]1[/SUB]), which alters immune responses to mammals, is one of the most common mycotoxins in feeds and food. Swine influenza virus (SIV) is a major pathogen of both animals and humans. However, there have been few studies about the relationship between AFB[SUB]1[/SUB] exposure and SIV replication. Here, for the first time, we investigated the involvement of AFB[SUB]1[/SUB] in SIV replication in vitro and in vivo and explored the underlying mechanism using multiple cell lines and mouse models. In vitro studies demonstrated that low concentrations of AFB[SUB]1[/SUB] (0.01-0.25 μg/ml) markedly promoted SIV replication as revealed by increased viral titers and matrix protein (M) mRNA and nucleoprotein (NP) levels in MDCK cells, A549 cells and PAMs. In vivo studies showed that 10-40 μg/kg of AFB[SUB]1[/SUB] exacerbated SIV infection in mice as illustrated by significantly higher lung virus titers, viral M mRNA levels, NP levels, lung indexes and more severe lung damage. Further study showed that AFB[SUB]1[/SUB] upregulated TLR4, but not other TLRs, in SIV-infected PAMs. Moreover, AFB[SUB]1[/SUB] activated TLR4 signaling as demonstrated by the increases of phosphorylated NFκB p65 and TNF-α release in PAMs and mice. In contrast, TLR4 knockdown or the use of BAY 11-7082, a specific inhibitor of NFκB, blocked the AFB[SUB]1[/SUB]-promoted SIV replication and inflammatory responses in PAMs. Furthermore, a TLR4-specific antagonist, TAK242, and TLR4 knockout both attenuated the AFB[SUB]1[/SUB]-promoted SIV replication, inflammation and lung damage in mice. We therefore conclude that AFB[SUB]1[/SUB] exposure aggravates SIV replication, inflammation and lung damage by activating TLR4-NFκB signaling.
[h=4]KEYWORDS:[/h] NFκB; TLR4; TNF-α; aflatoxin B1; inflammation; lung damage; replication; swine influenza virus
PMID: 30337931 PMCID: PMC6180208 DOI: 10.3389/fimmu.2018.02297