Caenorhabditis elegans LIN-24, a homolog of bacterial pore-forming toxin, protects the host from microbial infection

被引：1

作者：

Zhang, Huijie ^{[1
,2
,3
]}

Zeng, Weirong ^{[1
,2
,3
]}

Zhao, Ming-Ming ^{[4
]}

Wang, Jiali ^{[1
,2
,3
]}

Wang, Qiquan ^{[1
,2
,3
,4
]}

Chen, Ting ^{[1
,2
,3
]}

Zhang, Yuyan ^{[4
]}

Lee, Wenhui ^{[1
,2
,3
]}

Chen, Shenghan ^{[1
,2
,3
]}

Zhang, Yun ^{[4
,5
]}

Lan, Xinqiang ^{[1
,2
,3
,6
,7
,8
]}

Xiang, Yang ^{[1
,2
,3
,6
,7
,8
]}

机构：

[1] Nanchang Univ, Metab Control & Aging, Human Aging Res Inst HARI, Nanchang, Peoples R China

[2] Nanchang Univ, Sch Life Sci, Nanchang, Peoples R China

[3] Jiangxi Key Lab Human Aging, Nanchang, Peoples R China

[4] Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Key Lab Bioact Peptides Yunnan Prov, Kunming Inst Zool, Kunming, Peoples R China

[5] Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Key Lab Bioact Peptides Yunnan Prov, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China

[6] Nanchang Univ, Metab Control & Aging, Human Aging Res Inst HARI, Nanchang 330031, Jiangxi, Peoples R China

[7] Nanchang Univ, Sch Life Sci, Nanchang 330031, Jiangxi, Peoples R China

[8] Jiangxi Key Lab Human Aging, Nanchang 330031, Jiangxi, Peoples R China

来源：

FASEB JOURNAL | 2023年 / 37卷 / 10期

基金：

中国国家自然科学基金;

关键词：

aerolysin-like proteins; immune response; LIN-24; microbial infection; pore-forming toxin-like proteins; GENES; ZEBRAFISH; DAF-16;

D O I：

10.1096/fj.202300063R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aerolysin-like pore-forming protein (af-PFP) superfamily members are double-edge swords that assist the bacterial infection but shied bacteria from the host by various mechanisms in some species including the toad Bombina maxima and zebrafish. While members of this family are widely expressed in all kingdoms, especially non-bacteria species, it remains unclear whether their anti-bacterial function is conserved. LIN-24 is an af-PFP that is constitutively expressed throughout the Caenorhabditis elegans lifespan. Here, we observed that LIN-24 knockdown reduced the maximum lifespan of worms. RNA-seq analysis identified 323 differentially expressed genes (DEGs) post-LIN- 24 knockdown that were enriched in "immune response" and "lysosome pathway," suggesting a possible role for LIN-24 in resisting microbial infection. In line with this, we found that Pseudomonas aeruginosa 14 (PA14) infection induced LIN-24 expression, and that survival after PA14 infection was significantly reduced by LIN-24 knockdown. In contrast, LIN-24 overexpression (LIN-24-OE) conferred protection against PA14 infection, with worms showing longer survival time and reduced bacterial load. Weighted gene co-expression network analysis of LIN-24-OE worms showed that the highest correlation module was enriched in factors related to immunity and the defense response. Finally, by predicting transcription factors from RNA-seq data and knocking down candidate transcription factors in LIN-24-OE worms, we revealed that LIN-24 may protect worms against bacterial infection by stimulating DAF-16-mediated immune responses. These findings agree with our previous studies showing an anti-microbial role for the amphibian-derived af-PFP complex beta gamma-CAT, suggesting that af-PFPs may play a conserved role in combatting microbial infections. Further research is needed to determine the roles this protein family plays in other physio-pathological processes, such as metabolism, longevity, and aging.

引用

页数：14

共 46 条

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