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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-?B, 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.

SUBMITTER: Yue C

PROVIDER: S-EPMC6499186 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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

Yue Chaoxiong C Li Jinquan J Jin Hui H Hua Kexin K Zhou Wei W Wang Yueyi Y Cheng Guirong G Liu Dan D Xu Lang L Chen Yushan Y Zeng Yan Y

Frontiers in cellular and infection microbiology 20190416

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 ...[more]

PMID: 31106159

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Project description:Haemophilus parasuis is a commensal bacterium of the upper respiratory tract of healthy pigs. However, in conjunction with viral infections in immunocompromised animals H. parasuis can transform into a pathogen that is responsible for causing Glasser's disease which is typically characterized by fibrinous polyserositis, polyarthritis, meningitis and sometimes acute pneumonia and septicemia in pigs. Haemophilus parasuis serovar 5 is highly virulent and more frequently isolated from respiratory and systemic infection in pigs. Recently a highly virulent H. parasuis serovar 4 was isolated from the tissues of diseased pigs. To understand the differences in virulence and virulence-associated genes between H. parasuis serovar 5 and highly virulent H. parasuis serovar 4 strains, a genomic library was generated by TruSeq preparation and sequenced on Illumina HiSeq 2000 obtaining 50 bp PE reads. A three-way comparative genomic analysis was conducted between two highly virulent H. parasuis serovar 4 strains and H. parasuis serovar 5. Haemophilus parasuis serovar 5 GenBank isolate SH0165 (GenBank accession number CP001321.1) was used as reference strain for assembly. Results of these analysis revealed the highly virulent H. parasuis serovar 4 lacks genes encoding for, glycosyl transferases, polysaccharide biosynthesis protein capD, spore coat polysaccharide biosynthesis protein C, polysaccharide export protein and sialyltransferase which can modify the lipopolysaccharide forming a short-chain LPS lacking O-specific polysaccharide chains often referred to as lipooligosaccharide (LOS). In addition, it can modify the outer membrane protein (OMP) structure. The lack of sialyltransferase significantly reduced the amount of sialic acid incorporated into LOS, a major and essential component of the cell wall and an important virulence determinant. These molecules may be involved in various stages of pathogenesis through molecular mimicry and by causing host cell cytotoxicity, reduced inflammatory and immunological response to infection with this organism. The mechanism by which sialyation of LPS contributes to virulence is a key to understanding the pathogenesis of this highly virulent H. parasuis serovar 4. This analysis also revealed the presence of virulence associated genes similar to the MerR family transcriptional regulators, macrophage infectivity potentiator protein, hemolysin, opacity associated protein, toxin antitoxin system, and virulence associated protein D and colicins. Haemophilus parasuis serovar 4 variants also possess extensive metal ion uptake and regulation mechanism which controls various virulence and virulence associated genes. A combination of virulence associated factors and/or genes and proteins with overlapping functions may be responsible for the apparent enhanced virulence of this organism. The extensive structural modification of LOS and OMP of variant H. parasuis serovar 4 strains appear to aid in nasal colonization, are associated with the organisms' ability to evade the host immune response and provide serum-resistance. In addition, the combination of capsule modification and phase variation due to LOS substitutions could help variant H. parasuis serovar 4 transform into a highly virulent pathogen. Based on these results, the variant H. parasuis serovar 4 strains harbor a diverse repertoire of virulence associated genes which have not been previously reported.

Dataset Information

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

Publications

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

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