Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells

Abstract

Bacterial infections activate autophagy and autophagy restricts pathogens such as Haemophilus parasuis through specific mechanisms. Autophagy is associated with the pathogenesis of H. parasuis . However, the mechanisms have not been clarified. Here, we monitored autophagy processes using confocal microscopy, western blot, and transmission electron microscopy (TEM) and found that H. parasuis SH0165 (high-virulent strain) but not HN0001 (non-virulent strain) infection enhanced autophagy flux. The AMPK/mTOR autophagy pathway was required for autophagy initiation and ATG5, Beclin-1, ATG7, and ATG16L1 emerged as important components in the generation of the autophagosome during H. parasuis infection. Moreover, autophagy induced by H. parasuis SH0165 turned to fight against invaded bacteria and inhibit inflammation. Then we further demonstrated that autophagy blocked the production of the cytokines IL-8, CCL4, and CCL5 induced by SH0165 infection through the inhibition of NF-κB, p38, and JNK MAPK signaling pathway. Therefore, our findings suggest that autophagy may act as a cellular defense mechanism in response to H. parasuis and provide a new way that autophagy protects the host against H. parasuis infection.

Autophagy mediates ER stress and inflammation in Helicobacter pylori -related gastric cancer

“… 48 Previous studies on ATG16L1 silencing have demonstrated that the subsequent disruptive autophagy is associated with an elevated production of the important pro-inflammatory cytokine IL-8 in epithelial cells exposed to Shigella and Haemophilus parasuis SH0165. 24, 25 We demonstrated that while H. pylori induced IL-8 production in PBMCs, this was not affected by ATG16L1 rs2241880 status. In contrast, IL-8 production was significantly enhanced in GC cells harboring the GG-genotype.…”

“…The above findings were mostly corroborated at the protein level ( Figure 5(b )) and support the notion that disruptive autophagy promotes an increased IL-8 response in epithelial cells upon infection. 24 , 25

Figure 5. ATG16L1 rs2241880 status does not affect IL-8 production in immune cells but modulates IL-8 and TNF-α production in AGS cells upon infection with Helicobacter pylori .

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Effects of Trichinella spiralis and its excretory/secretory products on autophagy of host muscle cells in vivo and in vitro

“…Numerous studies demonstrated that autophagy could be triggered during microbial infection, such as bacteria, viruses, protozoa, and parasitic helminths [ 20 – 23 ]. However, autophagy induction has not been confirmed in Trichinella infection.…”

Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway

“…TEM experiments were conducted as the previous studies [19,34]. Samples were immersed in 1% osmium tetraoxide in PBS for 2h and then dehydrated in graded ethanol, and embedded in epoxy resin.…”